MFIB - Mutual Folding Induced by Binding
26-06-2017
MF2120001
Bacterial antidote ParD
2an7
NMR
homodimer
Escherichia coli
17656583
Oberer M, Zangger K, Gruber K, Keller W
The solution structure of ParD, the antidote of the ParDE toxin antitoxin module, provides the structural basis for DNA and toxin binding.
Protein Sci.
2007
8
16
1676-88
ParD is the antidote of the plasmid-encoded toxin-antitoxin (TA) system ParD-ParE. These modules rely on differential stabilities of a highly expressed but labile antidote and a stable toxin expressed from one operon. Consequently, loss of the coding plasmid results in loss of the protective antidote and poisoning of the cell. The antidote protein usually also exhibits an autoregulatory function of the operon. In this paper, we present the solution structure of ParD. The repressor activity of ParD is mediated by the N-terminal half of the protein, which adopts a ribbon-helix-helix (RHH) fold. The C-terminal half of the protein is unstructured in the absence of its cognate binding partner ParE. Based on homology with other RHH proteins, we present a model of the ParD-DNA interaction, with the antiparallel beta-strand being inserted into the major groove of DNA. The fusion of the N-terminal DNA-binding RHH motif to the toxin-binding unstructured C-terminal domain is discussed in its evolutionary context.
GO:0043565
sequence-specific DNA binding
GO:0042803
protein homodimerization activity
GO:0051290
protein heterotetramerization
GO:0006351
transcription, DNA-templated
GO:0030541
plasmid partitioning
GO:0045892
negative regulation of transcription, DNA-templated
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Other
Ribbon-helix-helix (RHH)
A
Antitoxin ParD
Escherichia coli
MSRLTIDMTDQQHQSLKALAALQGKTIKQYALERLFPGDADADQAWQELKTMLGNRINDGLAGKVSTKSVGEILDEELSGDRA
83
P22995
1
83
100%
UniRef90_P22995
1
83
secondary structure
beta
2
8
secondary structure
helix
10
23
secondary structure
helix
27
34
secondary structure
helix
42
52
pfam
PF09386.7
ParD
1
79
B
Antitoxin ParD
Escherichia coli
MSRLTIDMTDQQHQSLKALAALQGKTIKQYALERLFPGDADADQAWQELKTMLGNRINDGLAGKVSTKSVGEILDEELSGDRA
83
P22995
1
83
100%
UniRef90_P22995
1
83
secondary structure
beta
2
8
secondary structure
helix
10
23
secondary structure
helix
27
35
secondary structure
helix
42
49
pfam
PF09386.7
ParD
1
79
The interacting chains form a ribbon-helix-helix (RHH) structure (PMID:17656583). These structures in general have been described with the two monomers adopting a stable conformation upon the interaction (PMID:17676053). The hydrophobic core stabilizing the complex is formed by both interactors and is thus absent prior to the interaction (PMID:25713077).
MF2120002
Helicobacter pylori HP0222
1x93
NMR
homodimer
Helicobacter pylori
15723352
Popescu A, Karpay A, Israel DA, Peek RM, Krezel AM
Helicobacter pylori protein HP0222 belongs to Arc/MetJ family of transcriptional regulators.
Proteins
2005
2
59
303-11
Helicobacter pylori is a widespread human bacterial pathogen responsible for inducing gastric and duodenal ulcers and gastric cancers. To date, only 16 protein structures from this organism have been determined, and more than 30% of its 1500 protein functions remain unknown. We report the biochemical characterization, the tertiary structure determined by solution nuclear magnetic resonance (NMR) methods and the putative function of the previously uncharacterized protein HP0222 (JHP0208) from H. pylori. Recombinant HP0222 behaves as a dimer in crosslinking and size exclusion chromatography experiments. The structure consists of a ribbon-helix-helix fold characteristic of transcription factors of the Arc/MetJ family, which all bind DNA as higher order oligomers. Electrophoretic mobility shift assays reveal that HP0222 binds to double-stranded DNA. Previous studies have shown significant increases in transcription levels of HP0222 in response to acid shock and adherence to gastric epithelial cells. To assess possible involvement of HP0222 in acid resistance, we constructed and assayed an H. pylori HP0222 null mutant. We propose that HP0222 is a novel transcriptional regulator in H. pylori.
GO:0006355
regulation of transcription, DNA-templated
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Other
Ribbon-helix-helix (RHH)
A
Uncharacterized protein
Helicobacter pylori
TRAVSLYFSDEQYQKLEKMANEEEESVGSYIKRYILKALRKIEMRGSHHHHHHGS
55
O25010
31
73
58.9%
UniRef90_A0A060Q0Z2
31
77
secondary structure
beta
32
38
secondary structure
helix
40
52
secondary structure
helix
59
69
pfam
PF16777.2
RHH_7
1
73
B
Uncharacterized protein
Helicobacter pylori
TRAVSLYFSDEQYQKLEKMANEEEESVGSYIKRYILKALRKIEMRGSHHHHHHGS
55
O25010
31
73
58.9%
UniRef90_A0A060Q0Z2
31
77
secondary structure
beta
32
38
secondary structure
helix
40
52
secondary structure
helix
57
72
pfam
PF16777.2
RHH_7
1
73
The interacting chains form a ribbon-helix-helix (RHH) structure (PMID:15723352). These structures in general have been described with the two monomers adopting a stable conformation upon the interaction (PMID:17676053). The hydrophobic core stabilizing the complex is formed by both interactors and is thus absent prior to the interaction (PMID:25713077).
MF2120003
Helicobacter pylori JHP0511 (HP0564)
2k1o
NMR
homodimer
Helicobacter pylori
18623065
Borin BN, Krezel AM
Structure of HP0564 from Helicobacter pylori identifies it as a new transcriptional regulator.
Proteins
2008
1
73
265-8
No abstract available.
GO:0006355
regulation of transcription, DNA-templated
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Other
Ribbon-helix-helix (RHH)
A
Putative
Helicobacter pylori
MRGSHHHHHHGSKRNFSVTFYLSKEEHDVLRRLADEEVESVNSFVKRHILKTIIYKKGTNQDSSIN
66
Q9ZLR7
21
74
66.7%
UniRef90_B5Z6T5
21
74
secondary structure
beta
24
31
secondary structure
helix
32
43
secondary structure
helix
49
61
pfam
PF16777.2
RHH_7
2
66
B
Putative
Helicobacter pylori
MRGSHHHHHHGSKRNFSVTFYLSKEEHDVLRRLADEEVESVNSFVKRHILKTIIYKKGTNQDSSIN
66
Q9ZLR7
21
74
66.7%
UniRef90_B5Z6T5
21
74
secondary structure
beta
23
30
secondary structure
helix
32
43
secondary structure
helix
49
61
pfam
PF16777.2
RHH_7
2
66
The interacting chains form a ribbon-helix-helix (RHH) structure (PMID:18623065). These structures in general have been described with the two monomers adopting a stable conformation upon the interaction (PMID:17676053). The hydrophobic core stabilizing the complex is formed by both interactors and is thus absent prior to the interaction (PMID:25713077).
MF2120004
ParG
1p94
NMR
homodimer
Salmonella newport
14622405
Golovanov AP, Barillà D, Golovanova M, Hayes F, Lian LY
ParG, a protein required for active partition of bacterial plasmids, has a dimeric ribbon-helix-helix structure.
Mol. Microbiol.
2003
4
50
1141-53
The ParG protein (8.6 kDa) is an essential component of the DNA partition complex of multidrug resistance plasmid TP228. ParG is a dimer in solution, interacts with DNA sequences upstream of the parFG genes and also with the ParF partition protein both in the absence and presence of target DNA. Here, the solution nuclear magnetic resonance structure of ParG is reported. The ParG dimer is composed of a folded domain formed by two closely intertwined C-terminal parts (residues 33-76), and two highly mobile tails consisting of N-terminal regions (residues 1-32). The folded part of ParG has the ribbon-helix-helix (RHH) architecture similar to that of the Arc/MetJ superfamily of DNA-binding transcriptional repressors, although the primary sequence similarity is very low. ParG interacts with DNA predominantly via its folded domain; this interaction is coupled with ParG oligomerization. The dimeric RHH structure of ParG suggests that it binds to DNA by inserting the double-stranded beta-sheet into the major groove of DNA, in a manner similar to transcriptional repressors from the Arc/MetJ superfamily, and that ParG can function as a transcriptional repressor itself. A new classification of proteins belonging to the Arc/MetJ superfamily and ParG homologues is proposed, based on the location of a conserved positively charged residue at either the beginning or at the end of the beta-strand which forms part of the DNA recognition motif.
GO:0006355
regulation of transcription, DNA-templated
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Other
Ribbon-helix-helix (RHH)
A
Plasmid partition protein ParG
Salmonella newport
MSLEKAHTSVKKMTFGENRDLERVVTAPVSSGKIKRVNVNFDEEKHTRFKAACARKGTSITDVVNQLVDNWLKENE
76
Q9KJ82
1
76
100%
UniRef90_K3K332
1
76
secondary structure
helix
2
6
secondary structure
helix
23
25
secondary structure
beta
34
36
secondary structure
beta
39
42
secondary structure
helix
43
56
secondary structure
helix
60
74
pfam
PF09274.7
ParG
1
76
B
Plasmid partition protein ParG
Salmonella newport
MSLEKAHTSVKKMTFGENRDLERVVTAPVSSGKIKRVNVNFDEEKHTRFKAACARKGTSITDVVNQLVDNWLKENE
76
Q9KJ82
1
76
100%
UniRef90_K3K332
1
76
secondary structure
helix
6
8
secondary structure
helix
19
21
secondary structure
beta
34
37
secondary structure
beta
40
42
secondary structure
helix
43
56
secondary structure
helix
60
72
pfam
PF09274.7
ParG
1
76
The interacting chains form a ribbon-helix-helix (RHH) structure (PMID:14622405). These structures in general have been described with the two monomers adopting a stable conformation upon the interaction (PMID:17676053). The hydrophobic core stabilizing the complex is formed by both interactors and is thus absent prior to the interaction (PMID:25713077).
MF2100001
Human parathyroid hormone
1et1
X-ray
0.90
homodimer
Homo sapiens
10837469
Jin L, Briggs SL, Chandrasekhar S, Chirgadze NY, Clawson DK, Schevitz RW, Smiley DL, Tashjian AH, Zhang F
Crystal structure of human parathyroid hormone 1-34 at 0.9-A resolution.
J. Biol. Chem.
2000
35
275
27238-44
The N-terminal fragment 1-34 of parathyroid hormone (PTH), administered intermittently, results in increased bone formation in patients with osteoporosis. PTH and a related molecule, parathyroid hormone-related peptide (PTHrP), act on cells via a common PTH/PTHrP receptor. To define more precisely the ligand-receptor interactions, we have crystallized human PTH (hPTH)-(1-34) and determined the structure to 0.9-A resolution. hPTH-(1-34) crystallizes as a slightly bent, long helical dimer. Analysis reveals that the extended helical conformation of hPTH-(1-34) is the likely bioactive conformation. We have developed molecular models for the interaction of hPTH-(1-34) and hPTHrP-(1-34) with the PTH/PTHrP receptor. A receptor binding pocket for the N terminus of hPTH-(1-34) and a hydrophobic interface with the receptor for the C terminus of hPTH-(1-34) are proposed.
GO:0003705
transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding
GO:0031857
type 1 parathyroid hormone receptor binding
GO:0005179
hormone activity
GO:0051428
peptide hormone receptor binding
GO:0048873
homeostasis of number of cells within a tissue
GO:0045725
positive regulation of glycogen biosynthetic process
GO:0046326
positive regulation of glucose import
GO:0030819
positive regulation of cAMP biosynthetic process
GO:0034645
cellular macromolecule biosynthetic process
GO:0090290
positive regulation of osteoclast proliferation
GO:0045453
bone resorption
GO:0010288
response to lead ion
GO:0030501
positive regulation of bone mineralization
GO:0045471
response to ethanol
GO:0009967
positive regulation of signal transduction
GO:0042493
response to drug
GO:0071864
positive regulation of cell proliferation in bone marrow
GO:0071107
response to parathyroid hormone
GO:0000122
negative regulation of transcription from RNA polymerase II promoter
GO:0046686
response to cadmium ion
GO:0071774
response to fibroblast growth factor
GO:0006874
cellular calcium ion homeostasis
GO:0045944
positive regulation of transcription from RNA polymerase II promoter
GO:0046058
cAMP metabolic process
GO:0008628
hormone-mediated apoptotic signaling pathway
GO:0001501
skeletal system development
GO:0007266
Rho protein signal transduction
GO:0033280
response to vitamin D
GO:0071866
negative regulation of apoptotic process in bone marrow
GO:0007267
cell-cell signaling
GO:0007189
adenylate cyclase-activating G-protein coupled receptor signaling pathway
GO:0005615
extracellular space
GO:0005622
intracellular
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Other
Other
A
Parathyroid hormone
Homo sapiens
SVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHNF
34
P01270
32
65
29.6%
UniRef90_P01270
32
65
secondary structure
helix
34
64
pfam
PF01279.14
Parathyroid
29
112
B
Parathyroid hormone
Homo sapiens
SVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHNF
34
P01270
32
65
29.6%
UniRef90_P01270
32
65
secondary structure
helix
34
64
pfam
PF01279.14
Parathyroid
29
112
A
The 32-65 region described in DisProt entry DP00637 covers 100% of the sequence present in the structure.
B
The 32-65 region described in DisProt entry DP00637 covers 100% of the sequence present in the structure.
MF2200001
Human ribosomal protein P1-P2 heterodimer
4beh
NMR
heterodimer
Homo sapiens
23892290
Lee KM, Yusa K, Chu LO, Wing-Heng Yu C, Oono M, Miyoshi T, Ito K, Shaw PC, Wong KB, Uchiumi T
Solution structure of human P1*P2 heterodimer provides insights into the role of eukaryotic stalk in recruiting the ribosome-inactivating protein trichosanthin to the ribosome.
Nucleic Acids Res.
2013
Lateral ribosomal stalk is responsible for binding and recruiting translation factors during protein synthesis. The eukaryotic stalk consists of one P0 protein with two copies of P1•P2 heterodimers to form a P0(P1•P2)2 pentameric P-complex. Here, we have solved the structure of full-length P1•P2 by nuclear magnetic resonance spectroscopy. P1 and P2 dimerize via their helical N-terminal domains, whereas the C-terminal tails of P1•P2 are unstructured and can extend up to ∼125 Å away from the dimerization domains. (15)N relaxation study reveals that the C-terminal tails are flexible, having a much faster internal mobility than the N-terminal domains. Replacement of prokaryotic L10(L7/L12)4/L11 by eukaryotic P0(P1•P2)2/eL12 rendered Escherichia coli ribosome, which is insensitive to trichosanthin (TCS), susceptible to depurination by TCS and the C-terminal tail was found to be responsible for this depurination. Truncation and insertion studies showed that depurination of hybrid ribosome is dependent on the length of the proline-alanine rich hinge region within the C-terminal tail. All together, we propose a model that recruitment of TCS to the sarcin-ricin loop required the flexible C-terminal tail, and the proline-alanine rich hinge region lengthens this C-terminal tail, allowing the tail to sweep around the ribosome to recruit TCS.
GO:0005515
protein binding
GO:0070180
large ribosomal subunit rRNA binding
GO:0003735
structural constituent of ribosome
GO:0019083
viral transcription
GO:0000184
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
GO:0006413
translational initiation
GO:0002181
cytoplasmic translation
GO:0006364
rRNA processing
GO:0006614
SRP-dependent cotranslational protein targeting to membrane
GO:0006414
translational elongation
GO:0030687
preribosome, large subunit precursor
GO:0070062
extracellular exosome
GO:0005925
focal adhesion
GO:0022625
cytosolic large ribosomal subunit
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
2
Other
Other
A
60S acidic ribosomal protein P1
Homo sapiens
MASVSELACIYSALILHDDEVTVTEDKINALIKAAGVNVEPFWPGLFAKALANVNIGSLICNVGAGGPAPAAGAAPAGGPAPSTAAAPAEEKKVEAKKEESEESDDDMGFGLFD
114
P05386
1
114
100%
UniRef90_P05386
1
114
secondary structure
helix
4
16
secondary structure
helix
25
35
secondary structure
helix
42
50
secondary structure
helix
57
60
pfam
PF00428.16
Ribosomal_60s
22
113
B
60S acidic ribosomal protein P2
Homo sapiens
AMRYVASYLLAALGGNSSPSAKDIKKILDSVGIEADDDRLNKVISELNGKNIEDVIAQGIGKLASVPAGGAVAVSAAPGSAAPAAGSAPAAAEEKKDEKKEESEESDDDMGFGLFD
116
P05387
1
115
100%
UniRef90_P05387
1
115
secondary structure
beta
1
3
secondary structure
helix
4
12
secondary structure
helix
20
30
secondary structure
helix
36
46
secondary structure
helix
51
56
secondary structure
beta
63
63
secondary structure
beta
66
66
pfam
PF00428.16
Ribosomal_60s
17
114
A
A close homologue sharing the same Pfam domain (PF00428.16) has been experimentally characterized as disordered in DisProt entry DP00001.
B
A close homologue sharing the same Pfam domain (PF00428.16) has been experimentally characterized as disordered in DisProt entry DP00002.
2lbf
MF2100002
Dimerization domain of ribosomal protein P2
2w1o
NMR
homodimer
Homo sapiens
20385603
Lee KM, Yu CW, Chan DS, Chiu TY, Zhu G, Sze KH, Shaw PC, Wong KB
Solution structure of the dimerization domain of ribosomal protein P2 provides insights for the structural organization of eukaryotic stalk.
Nucleic Acids Res.
2010
15
38
5206-16
The lateral stalk of ribosome is responsible for kingdom-specific binding of translation factors and activation of GTP hydrolysis that drives protein synthesis. In eukaryotes, the stalk is composed of acidic ribosomal proteins P0, P1 and P2 that constitute a pentameric P-complex in 1: 2: 2 ratio. We have determined the solution structure of the N-terminal dimerization domain of human P2 (NTD-P2), which provides insights into the structural organization of the eukaryotic stalk. Our structure revealed that eukaryotic stalk protein P2 forms a symmetric homodimer in solution, and is structurally distinct from the bacterial counterpart L12 homodimer. The two subunits of NTD-P2 form extensive hydrophobic interactions in the dimeric interface that buries 2400 A(2) of solvent accessible surface area. We have showed that P1 can dissociate P2 homodimer spontaneously to form a more stable P1/P2 1 : 1 heterodimer. By homology modelling, we identified three exposed polar residues on helix-3 of P2 are substituted by conserved hydrophobic residues in P1. Confirmed by mutagenesis, we showed that these residues on helix-3 of P1 are not involved in the dimerization of P1/P2, but instead play a vital role in anchoring P1/P2 heterodimer to P0. Based on our results, models of the eukaryotic stalk complex were proposed.
GO:0003735
structural constituent of ribosome
GO:0070180
large ribosomal subunit rRNA binding
GO:0005515
protein binding
GO:0006414
translational elongation
GO:0006364
rRNA processing
GO:0006614
SRP-dependent cotranslational protein targeting to membrane
GO:0006413
translational initiation
GO:0002181
cytoplasmic translation
GO:0000184
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
GO:0019083
viral transcription
GO:0005925
focal adhesion
GO:0022625
cytosolic large ribosomal subunit
GO:0070062
extracellular exosome
GO:0016020
membrane
GO:0030687
preribosome, large subunit precursor
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Other
Other
A
60S acidic ribosomal protein P2
Homo sapiens
AMRYVASYLLAALGGNSSPSAKDIKKILDSVGIEADDDRLNKVISELNGKNIEDVIAQGIGKLASVPAGG
70
P05387
1
69
60%
UniRef90_P05387
1
66
secondary structure
helix
2
12
secondary structure
helix
20
30
secondary structure
helix
37
48
secondary structure
helix
51
58
secondary structure
helix
60
62
pfam
PF00428.16
Ribosomal_60s
17
114
B
60S acidic ribosomal protein P2
Homo sapiens
AMRYVASYLLAALGGNSSPSAKDIKKILDSVGIEADDDRLNKVISELNGKNIEDVIAQGIGKLASVPAGG
70
P05387
1
69
60%
UniRef90_P05387
1
66
secondary structure
helix
2
12
secondary structure
helix
20
30
secondary structure
helix
37
48
secondary structure
helix
51
58
secondary structure
helix
60
62
pfam
PF00428.16
Ribosomal_60s
17
114
A
A close homologue sharing the same Pfam domain (PF00428.16) has been experimentally characterized as disordered in DisProt entry DP00002.
B
A close homologue sharing the same Pfam domain (PF00428.16) has been experimentally characterized as disordered in DisProt entry DP00002.
MF2201001
Nuclear receptor coactivators CBP and ACTR
1kbh
NMR
heterodimer
Homo sapiens / Mus musculus
11823864
Demarest SJ, Martinez-Yamout M, Chung J, Chen H, Xu W, Dyson HJ, Evans RM, Wright PE
Mutual synergistic folding in recruitment of CBP/p300 by p160 nuclear receptor coactivators.
Nature
2002
6871
415
549-53
Nuclear hormone receptors are ligand-activated transcription factors that regulate the expression of genes that are essential for development, reproduction and homeostasis. The hormone response is mediated through recruitment of p160 receptor coactivators and the general transcriptional coactivator CBP/p300, which function synergistically to activate transcription. These coactivators exhibit intrinsic histone acetyltransferase activity, function in the remodelling of chromatin, and facilitate the recruitment of RNA polymerase II and the basal transcription machinery. The activities of the p160 coactivators are dependent on CBP. Both coactivators are essential for proper cell-cycle control, differentiation and apoptosis, and are implicated in cancer and other diseases. To elucidate the molecular basis of assembling the multiprotein activation complex, we undertook a structural and thermodynamic analysis of the interaction domains of CBP and the activator for thyroid hormone and retinoid receptors. Here we show that although the isolated domains are intrinsically disordered, they combine with high affinity to form a cooperatively folded helical heterodimer. Our study uncovers a unique mechanism, called 'synergistic folding', through which p160 coactivators recruit CBP/p300 to allow transmission of the hormonal signal to the transcriptional machinery.
GO:0003713
transcription coactivator activity
GO:0005515
protein binding
GO:0004402
histone acetyltransferase activity
GO:0006351
transcription, DNA-templated
GO:0016573
histone acetylation
GO:0045944
positive regulation of transcription from RNA polymerase II promoter
GO:0005654
nucleoplasm
GO:0005737
cytoplasm
GO:0000790
nuclear chromatin
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
2
Other
Other
A
Nuclear receptor coactivator 3
Homo sapiens
EGQSDERALLDQLHTLLSNTDATGLEEIDRALGIPELVNQGQALEPK
47
Q9Y6Q9
1045
1091
3.3%
UniRef90_Q9Y6Q9
1045
1091
secondary structure
helix
1049
1060
secondary structure
helix
1069
1075
secondary structure
helix
1078
1084
secondary structure
helix
1086
1088
pfam
PF08815.7
Nuc_rec_co-act
1045
1093
B
CREB-binding protein
Mus musculus
PNRSISPSALQDLLRTLKSPSSPQQQQQVLNILKSNPQLMAAFIKQRTAKYVANQPGMQ
59
P45481
2059
2117
2.4%
UniRef90_Q92793
2058
2116
secondary structure
helix
2067
2076
secondary structure
helix
2086
2091
secondary structure
helix
2095
2110
pfam
PF09030.7
Creb_binding
2019
2115
The interacting monomers have been described to undergo mutual synergistic folding upon binding (PMID:11823864).
A
The 1018-1088 region described in DisProt entry DP00343 and the 1018-1088 region described in IDEAL entry IID00110 cover 100% of the sequence present in the structure.
B
The 2059-2152 region described in DisProt entry DP00348 and the 2057-2117 region described in IDEAL entry IID50008 cover 100% of the sequence present in the structure.
MF4210001
L27 (Lin-2, Lin-7) domain complex (rat)
1rso
NMR
heterotetramer (dimer of dimers)
Rattus norvegicus
15048107
Feng W, Long JF, Fan JS, Suetake T, Zhang M
The tetrameric L27 domain complex as an organization platform for supramolecular assemblies.
Nat. Struct. Mol. Biol.
2004
5
11
475-80
L27 domain, initially identified in the Caenorhabditis elegans Lin-2 and Lin-7 proteins, is a protein interaction module that exists in a large family of scaffold proteins. The domain can function as an organization center of large protein assemblies required for establishment and maintenance of cell polarity. We have solved the high-resolution NMR structure of a tetrameric complex of L27 domains containing two SAP97-mLin-2 L27 domain heterodimers. Each L27 domain contains three a-helices. The first two helices of each domain are packed together to form a four-helical bundle in the heterodimer. The third helix of each L27 domain forms another four-helical bundle that assembles the two heterodimers into a tetramer. The structure of the complex provides a mechanistic explanation for L27 domain-mediated polymerization of scaffold proteins, a process that is crucial for the assembly of supramolecular complexes in asymmetric cells.
GO:0008022
protein C-terminus binding
GO:0030165
PDZ domain binding
GO:0042734
presynaptic membrane
GO:0005829
cytosol
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
2
L27 domains
L27_1 type
A
Disks large homolog 1
Rattus norvegicus
RKQDTQRALHLLEEYRSKLSQTEDRQLRSSIERVISIFQSNLFQALIDIQEFYEVTLLDN
60
Q62696
4
63
6.6%
UniRef90_Q12959
4
63
secondary structure
helix
5
20
secondary structure
helix
28
42
secondary structure
helix
44
52
secondary structure
beta
56
60
pfam
PF09058.7
L27_1
4
62
B
Peripheral plasma membrane protein CASK
Rattus norvegicus
GLLAAERAVSQVLDSLEEIHALTDSSEKDLDFLHSVFQDQHLHTLLDLYDKINTKS
56
Q62915
339
394
6.2%
UniRef90_O14936
339
394
secondary structure
helix
345
359
secondary structure
helix
365
376
secondary structure
helix
378
391
pfam
PF02828.13
L27
347
400
C
Disks large homolog 1
Rattus norvegicus
RKQDTQRALHLLEEYRSKLSQTEDRQLRSSIERVISIFQSNLFQALIDIQEFYEVTLLDN
60
Q62696
4
63
6.6%
UniRef90_Q12959
4
63
secondary structure
helix
5
20
secondary structure
helix
28
42
secondary structure
helix
44
53
secondary structure
beta
56
60
pfam
PF09058.7
L27_1
4
62
D
Peripheral plasma membrane protein CASK
Rattus norvegicus
GLLAAERAVSQVLDSLEEIHALTDSSEKDLDFLHSVFQDQHLHTLLDLYDKINTKS
56
Q62915
339
394
6.2%
UniRef90_O14936
339
394
secondary structure
helix
342
359
secondary structure
helix
365
376
secondary structure
helix
378
393
pfam
PF02828.13
L27
347
400
The interacting chains form a heterotetrameric L27 complex (PMID:15048107). L27 complexes formed by Lin-2 and Lin-7 proteins were shown to function as obligate heterodimers/tetramers undergoing a cooperative unfolding transition. Circular dichroism studies reveal that the individual monomers are largely unfolded outside the complex form (PMID:12110687).
MF2201002
CBP nuclear coactivator binding domain in complex with p53 TAD
2l14
NMR
heterodimer
Mus musculus / Homo sapiens
20961098
Lee CW, Martinez-Yamout MA, Dyson HJ, Wright PE
Structure of the p53 transactivation domain in complex with the nuclear receptor coactivator binding domain of CREB binding protein.
Biochemistry
2010
46
49
9964-71
The activity and stability of the tumor suppressor p53 are regulated by interactions with key cellular proteins such as MDM2 and CBP/p300. The transactivation domain (TAD) of p53 contains two subdomains (AD1 and AD2) and interacts directly with the N-terminal domain of MDM2 and with several domains of CBP/p300. Here we report the NMR structure of the full-length p53 TAD in complex with the nuclear coactivator binding domain (NCBD) of CBP. Both the p53 TAD and NCBD are intrinsically disordered and fold synergistically upon binding, as evidenced by the observed increase in helicity and increased level of dispersion of the amide proton resonances. The p53 TAD folds to form a pair of helices (denoted Pα1 and Pα2), which extend from Phe19 to Leu25 and from Pro47 to Trp53, respectively. In the complex, the NCBD forms a bundle of three helices (Cα1, residues 2066-2075; Cα2, residues 2081-2092; and Cα3, residues 2095-2105) with a hydrophobic groove into which p53 helices Pα1 and Pα2 dock. The polypeptide chain between the p53 helices remains flexible and makes no detectable intermolecular contacts with the NCBD. Complex formation is driven largely by hydrophobic contacts that form a stable intermolecular hydrophobic core. A salt bridge between D49 of p53 and R2105 of NCBD may contribute to the binding specificity. The structure provides the first insights into simultaneous binding of the AD1 and AD2 motifs to a target protein.
GO:0002039
p53 binding
GO:0001228
transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding
GO:0003684
damaged DNA binding
GO:0001085
RNA polymerase II transcription factor binding
GO:0003682
chromatin binding
GO:0008270
zinc ion binding
GO:0048511
rhythmic process
GO:0006366
transcription from RNA polymerase II promoter
GO:0045944
positive regulation of transcription from RNA polymerase II promoter
GO:0000122
negative regulation of transcription from RNA polymerase II promoter
GO:0034644
cellular response to UV
GO:0005737
cytoplasm
GO:0000790
nuclear chromatin
GO:0016605
PML body
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
2
Other
Other
A
CREB-binding protein
Mus musculus
PNRSISPSALQDLLRTLKSPSSPQQQQQVLNILKSNPQLMAAFIKQRTAKYVANQPGMQ
59
P45481
2059
2117
2.4%
UniRef90_Q92793
2058
2116
secondary structure
helix
2066
2075
secondary structure
helix
2081
2092
secondary structure
helix
2095
2106
pfam
PF09030.7
Creb_binding
2019
2115
B
Cellular tumor antigen p53
Homo sapiens
PLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGPD
49
P04637
13
61
12.5%
UniRef90_P04637
13
61
secondary structure
helix
19
25
secondary structure
helix
37
41
secondary structure
helix
47
53
pfam
PF08563.8
P53_TAD
5
29
A
The 2059-2152 region described in DisProt entry DP00348 and the 2057-2117 region described in IDEAL entry IID50008 cover 100% of the sequence present in the structure.
B
The 1-73 region described in DisProt entry DP00086 and the 1-96 region described in IDEAL entry IID00015 cover 100% of the sequence present in the structure.
MF2201003
P160/CREB-binding protein coactivator complex
2c52
NMR
heterodimer
Mus musculus / Homo sapiens
16540468
Waters L, Yue B, Veverka V, Renshaw P, Bramham J, Matsuda S, Frenkiel T, Kelly G, Muskett F, Carr M, Heery DM
Structural diversity in p160/CREB-binding protein coactivator complexes.
J. Biol. Chem.
2006
21
281
14787-95
Ligand-induced transcription by nuclear receptors involves the recruitment of p160 coactivators such as steroid receptor coactivator 1 (SRC1), in complex with histone acetyltransferases such as CREB-binding protein (CBP) and p300. Here we describe the solution structure of a complex formed by the SRC1 interaction domain (SID) of CBP and the activation domain (AD1) of SRC1, both of which contain four helical regions (Calpha1, Calpha2, Calpha3, and Calpha3' in CBP and Salpha1, Salpha2', Salpha2, and Salpha3 in SRC1). A tight four-helix bundle is formed between Salpha1, Calpha1, Calpha2, and Calpha3 that is capped by Salpha3. In contrast to the structure of the AD1 domain of the related p160 protein ACTR in complex with CBP SID, the sequences forming Salpha2' and Salpha2 in SRC1 AD1 are not involved in the interface between the two domains but rather serve to position Salpha3. Thus, although the CBP SID domain adopts a similar fold in complex with different p160 proteins, the topologies of the AD1 domains are strikingly different, a feature that is likely to contribute to functional specificity of these coactivator complexes.
GO:0003677
DNA binding
GO:0008134
transcription factor binding
GO:0004402
histone acetyltransferase activity
GO:0003682
chromatin binding
GO:0001105
RNA polymerase II transcription coactivator activity
GO:0006351
transcription, DNA-templated
GO:0045944
positive regulation of transcription from RNA polymerase II promoter
GO:0005737
cytoplasm
GO:0000790
nuclear chromatin
GO:0005654
nucleoplasm
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
2
Other
Other
A
CREB-binding protein
Mus musculus
PNRSISPSALQDLLRTLKSPSSPQQQQQVLNILKSNPQLMAAFIKQRTAKYVANQPGMQ
59
P45481
2059
2117
2.4%
UniRef90_Q92793
2058
2116
secondary structure
helix
2067
2075
secondary structure
helix
2082
2093
secondary structure
helix
2095
2106
pfam
PF09030.7
Creb_binding
2019
2115
B
Nuclear receptor coactivator 1
Homo sapiens
PTTVEGRNDEKALLEQLVSFLSGKDETELAELDRALGIDKLVQGGGLDVLSKLVPRGSL
59
Q15788
920
974
3.8%
UniRef90_Q15788
920
974
secondary structure
helix
929
941
secondary structure
helix
945
947
secondary structure
helix
952
954
pfam
PF08815.7
Nuc_rec_co-act
924
971
A
The 2059-2152 region described in DisProt entry DP00348 and the 2057-2117 region described in IDEAL entry IID50008 cover 100% of the sequence present in the structure.
B
A close homologue sharing the same Pfam domain (PF08815.7) has been experimentally characterized as disordered in DisProt entry DP00343 and IDEAL entry IID00110.
MF4120001
YefM antitoxin (Mycobacterium tuberculosis)
3cto
X-ray
2.50
homotetramer
Mycobacterium tuberculosis
18793646
Kumar P, Issac B, Dodson EJ, Turkenburg JP, Mande SC
Crystal structure of Mycobacterium tuberculosis YefM antitoxin reveals that it is not an intrinsically unstructured protein.
J. Mol. Biol.
2008
3
383
482-93
Toxin-antitoxin modules are present on chromosomes of almost all free-living prokaryotes. Some are implicated to act as stress-responsive elements, among their many functional roles. The YefM-YoeB toxin-antitoxin system is present in many bacterial species, where YefM belongs to the Phd family antidote of phage P1, whereas YoeB is a homolog of the RelE toxin of the RelBE system, rather than the Doc system of phage P1. YoeB, a ribonuclease, is believed to be conformationally stable, whereas YefM has been proposed to be a member of intrinsically disordered proteins. The ribonucleolytic activity of YoeB is neutralized by YefM upon formation of the YefM-YoeB complex. We report here the crystal structure of Mycobacterium tuberculosis YefM from two crystal isoforms. Our crystallographic and biophysical studies reveal that YefM is not an intrinsically unfolded protein and instead forms a well-defined structure with significant secondary and tertiary structure conformations. The residues involved in core formation of the folded structure are evolutionarily conserved among many bacterial species, supporting our observation. The C-terminal end of its polypeptide is highly pliable, which adopts different conformations in different monomers. Since at the physiological level YefM controls the activity of YoeB through intricate protein-protein interactions, the conformational heterogeneity in YefM revealed by our structure suggests that these might act a master switch in controlling YoeB activity.
GO:0003677
DNA binding
GO:0006355
regulation of transcription, DNA-templated
GO:0006351
transcription, DNA-templated
Chain E has been removed, as it is possibly a fragment of one of the chains forming the tetramer and is not involved in molecular interactions stabilizing the complex
4
1
Other
Phd antitoxin
A
Antitoxin RelJ
Mycobacterium tuberculosis
MSISASEARQRLFPLIEQVNTDHQPVRITSRAGDAVLMSADDYDAWQETVYLLRSPENARRLMEAVARDKAGHSAFTKSVDELREMAGGEE
91
P9WF24
1
91
100%
UniRef90_P9WF24
1
91
secondary structure
beta
2
4
secondary structure
helix
5
10
secondary structure
helix
12
22
secondary structure
beta
26
29
secondary structure
beta
35
39
secondary structure
helix
40
52
secondary structure
helix
56
67
pfam
PF02604.16
PhdYeFM_antitox
1
72
B
Antitoxin RelJ
Mycobacterium tuberculosis
MSISASEARQRLFPLIEQVNTDHQPVRITSRAGDAVLMSADDYDAWQETVYLLRSPENARRLMEAVARDKAGHSAFTKSVDELREMAGGEE
91
P9WF24
1
91
100%
UniRef90_P9WF24
1
91
secondary structure
beta
3
4
secondary structure
helix
5
10
secondary structure
helix
12
19
secondary structure
beta
26
29
secondary structure
beta
35
39
secondary structure
helix
40
52
secondary structure
helix
58
71
secondary structure
helix
73
83
pfam
PF02604.16
PhdYeFM_antitox
1
72
C
Antitoxin RelJ
Mycobacterium tuberculosis
MSISASEARQRLFPLIEQVNTDHQPVRITSRAGDAVLMSADDYDAWQETVYLLRSPENARRLMEAVARDKAGHSAFTKSVDELREMAGGEE
91
P9WF24
1
91
100%
UniRef90_P9WF24
1
91
secondary structure
beta
2
4
secondary structure
helix
5
10
secondary structure
helix
12
22
secondary structure
beta
26
29
secondary structure
beta
35
39
secondary structure
helix
40
52
secondary structure
helix
56
68
secondary structure
helix
70
85
pfam
PF02604.16
PhdYeFM_antitox
1
72
D
Antitoxin RelJ
Mycobacterium tuberculosis
MSISASEARQRLFPLIEQVNTDHQPVRITSRAGDAVLMSADDYDAWQETVYLLRSPENARRLMEAVARDKAGHSAFTKSVDELREMAGGEE
91
P9WF24
1
91
100%
UniRef90_P9WF24
1
91
secondary structure
beta
3
4
secondary structure
helix
5
10
secondary structure
helix
12
22
secondary structure
beta
26
29
secondary structure
beta
35
39
secondary structure
helix
40
52
secondary structure
helix
56
63
pfam
PF02604.16
PhdYeFM_antitox
1
72
The dimerization of the prevents host death (phd) antitoxin from Escherichia virus P1 has been shown with differential scanning calorimetry to fit well to a two-state model consisting of a dimer unfolding into monomer species (PMID:20603017).
A
A close homologue sharing the same Pfam domain (PF02604.16) has been experimentally characterized as disordered in DisProt entry DP00288.
B
A close homologue sharing the same Pfam domain (PF02604.16) has been experimentally characterized as disordered in DisProt entry DP00288.
C
A close homologue sharing the same Pfam domain (PF02604.16) has been experimentally characterized as disordered in DisProt entry DP00288.
D
A close homologue sharing the same Pfam domain (PF02604.16) has been experimentally characterized as disordered in DisProt entry DP00288.
3d55
3oei
MF2140001
Arc repressor
1arq
NMR
homodimer
Enterobacteria phage P22
8107113
Bonvin AM, Vis H, Breg JN, Burgering MJ, Boelens R, Kaptein R
Nuclear magnetic resonance solution structure of the Arc repressor using relaxation matrix calculations.
J. Mol. Biol.
1994
1
236
328-41
The Arc repressor of Salmonella bacteriophage P22 is a dimeric sequence-specific DNA-binding protein. The solution structure of Arc has been determined from 2D NMR data using an "ensemble" iterative relaxation matrix approach (IRMA) followed by direct NOE refinement with DINOSAUR. A set of 51 structures was generated with distance geometry and further refined with a combination of restrained energy minimization and restrained molecular dynamics in a parallel refinement protocol. Distance constraints were obtained from an extensive set of NOE build-ups in H2O and 2H2O via relaxation matrix calculations from the ensemble of structures. Methyl group rotation, aromatic ring flaps and internal mobility effects (via order parameters obtained from a free molecular dynamics run in water) were included in these calculations. The best structures were finally refined with direct NOE constraints following a slow-cooling simulated annealing protocol. In this final refinement stage, theoretical NOE intensities were directly compared with the experimental data and forces were derived using a simple two-spin approximation for the gradient of the NOE function. Dynamic assignment was applied to the peaks involving unassigned diastereotopic groups. The structure is determined to a precision (r.m.s.d. from the average excluding the ill defined C and N-terminal region) of 0.55 and 1.10 A for backbone and all atoms, respectively. The final structures, with R factor values around 0.35, have good stereochemical qualities, contain an extensive network of hydrogen bonds consistent with the secondary structure elements and structural features in concordance with genetic data. The overall folding of the solution and crystal structures is the same.
GO:0003677
DNA binding
GO:0006351
transcription, DNA-templated
GO:0006355
regulation of transcription, DNA-templated
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Other
Ribbon-helix-helix (RHH)
A
Transcriptional repressor arc
Enterobacteria phage P22
MKGMSKMPQFNLRWPREVLDLVRKVAEENGRSVNSEIYQRVMESFKKEGRIGA
53
P03050
1
53
100%
UniRef90_P03050
1
53
secondary structure
beta
9
13
secondary structure
helix
16
29
secondary structure
helix
33
45
secondary structure
helix
49
52
pfam
PF03869.11
Arc
4
53
B
Transcriptional repressor arc
Enterobacteria phage P22
MKGMSKMPQFNLRWPREVLDLVRKVAEENGRSVNSEIYQRVMESFKKEGRIGA
53
P03050
1
53
100%
UniRef90_P03050
1
53
secondary structure
beta
9
13
secondary structure
helix
16
29
secondary structure
helix
34
47
pfam
PF03869.11
Arc
4
53
The Arc repressor protein has been experimentally shown to be a molten globule in monomeric form (PMID:8446590, PMID:7696567). Adopting the proper three dimensional structure is linked to dimerization (PMID:8110744, PMID:10889040).
1arr
1b28
1baz
1bdt
1bdv
1myk
1myl
1nla
1par
1qtg
MF2120005
Trp repressor protein (Ruminococcus obeum)
3frw
X-ray
2.05
homodimer
Blautia obeum ATCC 29174
Osipiuk, J., Keigher, L., Jedrzejczak, R., Babnigg, G., Joachimiak, A.
X-ray crystal structure of putative TrpR protein from Ruminococcus obeum.
To be published
-
GO:0003700
transcription factor activity, sequence-specific DNA binding
GO:0043565
sequence-specific DNA binding
GO:0006355
regulation of transcription, DNA-templated
GO:0005622
intracellular
Chains C,D,E,F,G and H were removed as chains A and B represent the biologically active dimer.
2
1
Other
Trp repressor-like
A
TrpR family protein YerC/YecD
Blautia obeum ATCC 29174
SNAMGKKIRTEEVDHLFEAILCLKNKEECYTFFEDVCTINELLSLSQRFEVAKMLTDKRTYLDISEKTGASTATISRVNRSLNYGNDGYEMVFSRMKEKETAGKTEE
107
A5ZMD8
1
104
100%
UniRef90_D4LQW8
1
104
secondary structure
helix
8
18
secondary structure
helix
23
33
secondary structure
helix
36
50
secondary structure
helix
52
54
secondary structure
helix
59
66
secondary structure
helix
70
82
secondary structure
helix
86
87
secondary structure
helix
89
92
secondary structure
helix
94
98
pfam
PF01371.16
Trp_repressor
8
94
B
TrpR family protein YerC/YecD
Blautia obeum ATCC 29174
SNAMGKKIRTEEVDHLFEAILCLKNKEECYTFFEDVCTINELLSLSQRFEVAKMLTDKRTYLDISEKTGASTATISRVNRSLNYGNDGYEMVFSRMKEKETAGKTEE
107
A5ZMD8
1
104
100%
UniRef90_D4LQW8
1
104
secondary structure
helix
8
18
secondary structure
helix
23
33
secondary structure
helix
36
50
secondary structure
helix
52
54
secondary structure
helix
59
66
secondary structure
helix
70
82
secondary structure
helix
86
87
secondary structure
helix
89
92
secondary structure
helix
94
97
pfam
PF01371.16
Trp_repressor
8
94
The folding and dimerization of the Trp repressor were shown to be linked by both experimental (PMID:10329154, PMID:2223756, PMID:7578063) and computational studies (PMID:10465773).
MF2120006
Transcriptional repressor CopG
2cpg
X-ray
1.60
homodimer
Streptococcus agalactiae
9857196
Gomis-Rüth FX, Solá M, Acebo P, Párraga A, Guasch A, Eritja R, González A, Espinosa M, del Solar G, Coll M
The structure of plasmid-encoded transcriptional repressor CopG unliganded and bound to its operator.
EMBO J.
1998
24
17
7404-15
The structure of the 45 amino acid transcriptional repressor, CopG, has been solved unliganded and bound to its target operator DNA. The protein, encoded by the promiscuous streptococcal plasmid pMV158, is involved in the control of plasmid copy number. The structure of this protein repressor, which is the shortest reported to date and the first isolated from a plasmid, has a homodimeric ribbon-helix-helix arrangement. It is the prototype for a family of homologous plasmid repressors. CopG cooperatively associates, completely protecting several turns on one face of the double helix in both directions from a 13-bp pseudosymmetric primary DNA recognition element. In the complex structure, one protein tetramer binds at one face of a 19-bp oligonucleotide, containing the pseudosymmetric element, with two beta-ribbons inserted into the major groove. The DNA is bent 60 degrees by compression of both major and minor grooves. The protein dimer displays topological similarity to Arc and MetJ repressors. Nevertheless, the functional tetramer has a unique structure with the two vicinal recognition ribbon elements at a short distance, thus inducing strong DNA bend. Further structural resemblance is found with helix-turn-helix regions of unrelated DNA-binding proteins. In contrast to these, however, the bihelical region of CopG has a role in oligomerization instead of DNA recognition. This observation unveils an evolutionary link between ribbon-helix-helix and helix-turn-helix proteins.
GO:0003677
DNA binding
GO:0006351
transcription, DNA-templated
GO:0006276
plasmid maintenance
GO:0006355
regulation of transcription, DNA-templated
Chain C has been removed as chains A and B represent the biologically active dimer.
2
1
Other
Ribbon-helix-helix (RHH)
A
Protein CopG
Streptococcus agalactiae
MKKRLTITLSESVLENLEKMAREMGLSKSAMISVALENYKKGQER
45
P13920
1
45
100%
UniRef90_P13920
1
45
secondary structure
beta
2
10
secondary structure
helix
11
24
secondary structure
helix
28
41
pfam
PF01402.18
RHH_1
4
41
B
Protein CopG
Streptococcus agalactiae
MKKRLTITLSESVLENLEKMAREMGLSKSAMISVALENYKKGQER
45
P13920
1
45
100%
UniRef90_P13920
1
45
secondary structure
beta
2
10
secondary structure
helix
11
24
secondary structure
helix
28
43
pfam
PF01402.18
RHH_1
4
41
The interacting chains form a ribbon-helix-helix (RHH) structure (PMID:17656583). These structures in general have been described with the two monomers adopting a stable conformation upon the interaction (PMID:9857196). The hydrophobic core stabilizing the complex is formed by both interactors and is thus absent prior to the interaction (PMID:25713077). Furthermore, CopG was directly shown to associate and fold cooperatively via a two state folding and binding process (PMID:9857196, PMID:15169951).
1b01
1ea4
MF2120007
UmuD' protein filament
1ay9
X-ray
3.00
homodimer
Escherichia coli O157:H7
8994967
Peat TS, Frank EG, McDonald JP, Levine AS, Woodgate R, Hendrickson WA
The UmuD' protein filament and its potential role in damage induced mutagenesis.
Structure
1996
12
4
1401-12
CONCLUSIONS: The activation of UmuD to UmuD' appears to cause a large conformational change in the protein which allows it to form oligomers in solution at physiologically relevant concentrations. Properties of these oligomers are consistent with the filament structures seen in crystals of UmuD'. RESULTS: Recent X-ray crystallographic analysis shows that in addition to forming molecular dimers, the N- and C-terminal tails of UmuD' extend from a globular beta structure to associate and produce crystallized filaments. We have investigated this phenomenon and find that these filaments appear to relate to biological activity. Higher order oligomers are found in solution with UmuD', but not with UmuD nor with a mutant of UmuD' lacking the extended N terminus. Deletion of the N terminus of UmuD' does not affect its ability to form molecular dimers but does severely compromise its ability to interact with a RecA-DNA filament and to participate in mutagenesis. Mutations in the C terminus of UmuD' result in both gain and loss of function for mutagenesis. BACKGROUND: Damage induced 'SOS mutagenesis' may occur transiently as part of the global SOS response to DNA damage in bacteria. A key participant in this process is the UmuD protein, which is produced in an inactive from but converted to the active form, UmuD', by a RecA-mediated self-cleavage reaction. UmuD', together with UmuC and activated RecA (RecA*), enables the DNA polymerase III holoenzyme to replicate across chemical and UV induced lesions. The efficiency of this reaction depends on several intricate protein-protein interactions.
GO:0008236
serine-type peptidase activity
GO:0003677
DNA binding
GO:0006281
DNA repair
GO:0006355
regulation of transcription, DNA-templated
GO:0009432
SOS response
GO:0006508
proteolysis
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Other
Other
A
Protein UmuD
Escherichia coli O157:H7
DYVEQRIDLNQLLIQHPSATYFVKASGDSMIDGGISDGDLLIVDSAITASHGDIVIAAVDGEFTVKKLQLRPTVQLIPMNSAYSPITISSEDTLDVFGVVIHVVKAMR
108
P0AG12
32
139
77.7%
UniRef90_P0AG12
32
139
secondary structure
helix
40
44
secondary structure
helix
48
50
secondary structure
beta
51
55
secondary structure
helix
62
64
secondary structure
beta
71
75
secondary structure
beta
85
90
secondary structure
beta
93
100
secondary structure
beta
106
108
secondary structure
beta
117
118
secondary structure
beta
125
135
pfam
PF00717.20
Peptidase_S24
55
122
B
Protein UmuD
Escherichia coli O157:H7
DYVEQRIDLNQLLIQHPSATYFVKASGDSMIDGGISDGDLLIVDSAITASHGDIVIAAVDGEFTVKKLQLRPTVQLIPMNSAYSPITISSEDTLDVFGVVIHVVKAMR
108
P0AG12
32
139
77.7%
UniRef90_P0AG12
32
139
secondary structure
helix
40
44
secondary structure
helix
48
50
secondary structure
beta
51
55
secondary structure
helix
62
64
secondary structure
beta
71
75
secondary structure
beta
85
90
secondary structure
beta
93
100
secondary structure
beta
106
108
secondary structure
beta
117
118
secondary structure
beta
125
135
pfam
PF00717.20
Peptidase_S24
55
122
A
The 1-139 region described in DisProt entry DP00626 covers 100% of the sequence present in the structure.
B
The 1-139 region described in DisProt entry DP00626 covers 100% of the sequence present in the structure.
1i4v
1umu
MF4100001
Transthyretin (human)
3a4d
X-ray
2.00
homotetramer (dimer of dimers)
Homo sapiens
19950966
Miyata M, Sato T, Mizuguchi M, Nakamura T, Ikemizu S, Nabeshima Y, Susuki S, Suwa Y, Morioka H, Ando Y, Suico MA, Shuto T, Koga T, Yamagata Y, Kai H
Role of the glutamic acid 54 residue in transthyretin stability and thyroxine binding.
Biochemistry
2010
1
49
114-23
Transthyretin (TTR) is a tetrameric protein associated with amyloidosis caused by tetramer dissociation and monomer misfolding. The structure of two TTR variants (E54G and E54K) with Glu54 point mutation that cause clinically aggressive amyloidosis remains unclear, although amyloidogenicity of artificial triple mutations (residues 53-55) in beta-strand D had been investigated. Here we first analyzed the crystal structures and biochemical and biophysical properties of E54G and E54K TTRs. The direction of the Lys15 side chain in E54K TTR and the surface electrostatic potential in the edge region in both variants were different from those of wild-type TTR. The presence of Lys54 leads to destabilization of tetramer structure due to enhanced electrostatic repulsion between Lys15 of two monomers. Consistent with structural data, the biochemical analyses demonstrated that E54G and E54K TTRs were more unstable than wild-type TTR. Furthermore, the entrance of the thyroxine (T(4)) binding pocket in TTR was markedly narrower in E54K TTR and wider in E54G TTR compared with wild-type TTR. The tetramer stabilization and amyloid fibril formation assays in the presence of T(4) showed lower tetramer stability and more fibril formation in E54K and E54G TTRs than in wild-type TTR, suggesting decreased T(4) binding to the TTR variants. These findings indicate that structural modification by Glu54 point mutation may sufficiently alter tetramer stability and T(4) binding.
GO:0046982
protein heterodimerization activity
GO:0005179
hormone activity
GO:0042802
identical protein binding
GO:0070324
thyroid hormone binding
GO:0042572
retinol metabolic process
GO:0030198
extracellular matrix organization
GO:0044267
cellular protein metabolic process
GO:0006810
transport
GO:0005737
cytoplasm
GO:0070062
extracellular exosome
GO:0005615
extracellular space
GO:0043234
protein complex
Chains C and D were generated from chains A and B respectively, using the biomatrices described in the original PDB file.
4
1
Transthyretin-like folds
Transthyretin
A
Transthyretin
Homo sapiens
GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE
127
P02766
21
147
86.4%
UniRef90_P02766
21
147
secondary structure
beta
32
38
secondary structure
beta
43
44
secondary structure
beta
49
55
secondary structure
beta
61
68
secondary structure
beta
74
75
secondary structure
beta
87
93
secondary structure
helix
95
101
secondary structure
beta
108
117
secondary structure
beta
124
132
secondary structure
beta
135
143
pfam
PF00576.18
Transthyretin
32
139
B
Transthyretin
Homo sapiens
GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE
127
P02766
21
147
86.4%
UniRef90_P02766
21
147
secondary structure
beta
32
38
secondary structure
beta
43
44
secondary structure
beta
49
55
secondary structure
beta
61
68
secondary structure
beta
74
75
secondary structure
beta
87
93
secondary structure
helix
95
101
secondary structure
beta
108
117
secondary structure
beta
124
132
secondary structure
beta
135
143
pfam
PF00576.18
Transthyretin
32
139
C
Transthyretin
Homo sapiens
GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE
127
P02766
21
147
86.4%
UniRef90_P02766
21
147
secondary structure
beta
32
38
secondary structure
beta
43
44
secondary structure
beta
49
55
secondary structure
beta
61
68
secondary structure
beta
74
75
secondary structure
beta
87
93
secondary structure
helix
95
101
secondary structure
beta
108
117
secondary structure
beta
124
132
secondary structure
beta
135
143
pfam
PF00576.18
Transthyretin
32
139
D
Transthyretin
Homo sapiens
GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE
127
P02766
21
147
86.4%
UniRef90_P02766
21
147
secondary structure
beta
32
38
secondary structure
beta
43
44
secondary structure
beta
49
55
secondary structure
beta
61
68
secondary structure
beta
74
75
secondary structure
beta
87
93
secondary structure
helix
95
101
secondary structure
beta
108
117
secondary structure
beta
124
132
secondary structure
beta
135
143
pfam
PF00576.18
Transthyretin
32
139
Transthyretin was shown in calorimetrics experiments to follow two-state folding/binding kinetics with the emergence of structure being linked to oligomerization (PMID:11152276).
1bm7
1bmz
1bz8
1bzd
1bze
1dvq
1dvs
1dvt
1dvu
1dvx
1dvy
1dvz
1e3f
1e4h
1e5a
1eta
1etb
1f41
1f86
1fh2
1fhn
1g1o
1gko
1ict
1iii
1iik
1ijn
1qab
1qwh
1rlb
1sok
1soq
1tha
1thc
1tlm
1tsh
1tt6
1tta
1ttb
1ttc
1ttr
1tyr
1tz8
1u21
1x7s
1x7t
1y1d
1z7j
1zcr
1zd6
2b14
2b15
2b16
2b77
2b9a
2f7i
2f8i
2fbr
2flm
2g3x
2g3z
2g4e
2g4g
2g5u
2g9k
2gab
2h4e
2nbo
2nbp
2noy
2pab
2qel
2qgb
2qgc
2qgd
2qge
2rox
2roy
2trh
2try
2wqa
3a4e
3a4f
3b56
3bsz
3bt0
3cbr
3cfm
3cfn
3cfq
3cft
3cn0
3cn1
3cn2
3cn3
3cn4
3cxf
3d2t
3d7p
3dgd
3did
3djr
3djs
3djt
3djz
3dk0
3dk2
3do4
3esn
3eso
3esp
3fc8
3fcb
3glz
3gps
3grb
3grg
3gs0
3gs4
3gs7
3hj0
3i9a
3i9i
3i9p
3imr
3ims
3imt
3imu
3imv
3imw
3ipb
3ipe
3kgs
3kgt
3kgu
3m1o
3nee
3neo
3nes
3nex
3ng5
3ozk
3ozl
3p3r
3p3s
3p3t
3p3u
3ssg
3tct
3tfb
3u2i
3u2j
3w3b
4abq
4abu
4abv
4abw
4ac2
4ac4
4act
4ank
4d7b
4der
4des
4det
4deu
4dew
4fi6
4fi7
4fi8
4hiq
4his
4hjs
4hjt
4hju
4i85
4i87
4i89
4iiz
4ik6
4ik7
4iki
4ikj
4ikk
4ikl
4ky2
4l1s
4l1t
4mas
4mrb
4mrc
4n85
4n86
4n87
4pm1
4pme
4pmf
4pvl
4pvm
4pvn
4pwe
4pwf
4pwg
4pwh
4pwi
4pwj
4pwk
4qrf
4qxv
4qya
4tkw
4tl4
4tl5
4tlk
4tls
4tlt
4tlu
4tm9
4tne
4tnf
4tng
4tq8
4tqh
4tqi
4tqp
4wnj
4wns
4wo0
4y9b
4y9c
4y9e
4y9f
4y9g
4ydm
4ydn
5a6i
5aks
5akt
5akv
5al0
5al8
5ayt
5boj
5clx
5cly
5clz
5cm1
5cn3
5cnh
5cr1
5dej
5dwp
5e23
5e4a
5e4o
5en3
5ezp
5fo2
5fw6
5fw7
5fw8
5hjg
5ihh
5jid
5jim
5jiq
5k1j
5k1n
5l4f
5l4i
5l4j
5l4m
5ttr
MF4110001
Transthyretin (rat)
1gke
X-ray
2.50
homotetramer (dimer of dimers)
Rattus norvegicus
9511961
Wojtczak A
Crystal structure of rat transthyretin at 2.5 A resolution: first report on a unique tetrameric structure.
Acta Biochim. Pol.
1997
3
44
505-17
The first observation of a unique tetrameric molecular structure of transthyretin from rat (rTTR, prealbumin) is reported. The structure has been determined by X-ray diffraction using molecular replacement and the structure of human transthyretin (hTTR) as a starting model. Crystals of native rat transthyretin are tetragonal, space group P4(3)2(1)2, and have four independent monomers in the asymmetric unit of the crystal lattice. Data were collected to 2.5 A resolution and the structure has been refined to R = 18.9% for 13584 data points between 8-2.5 A resolution. Like hTTR, the rat protein is also a 54000 Da tetramer with four identical polypeptide chains of 127 amino-acid residues. Of the 22 amino-acid residues which are different in the human and rat TTR sequences, none are in the thyroxine binding domain. Analysis of these data reveal that the tertiary structure of rTTR is similar to that of hTTR with only small differences in the flexible loop regions on the surface of the protein. As a result of local changes in flexible loop regions near residues 30-41, 60-65 and 102-104, the structure of rTTR monomers is more compact than that of the corresponding hTTR monomers. The loop between residues 30-41 is bound closer to the monomer core in the former as compared with the latter structure and there is a wider opening of the space formed between these loops at two adjacent monomeric subunits. These conformational changes do not affect the interfaces between the monomeric subunits and are not transmitted to the thyroxine binding site so that its topology remains not altered.
GO:0005179
hormone activity
GO:0046982
protein heterodimerization activity
GO:0070324
thyroid hormone binding
GO:0042802
identical protein binding
GO:0042572
retinol metabolic process
GO:0070327
thyroid hormone transport
GO:0042403
thyroid hormone metabolic process
GO:0005615
extracellular space
GO:0070062
extracellular exosome
GO:0043234
protein complex
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
1
Transthyretin-like folds
Transthyretin
A
Transthyretin
Rattus norvegicus
SKCPLMVKVLDAVRGSPAVDVAVKVFKKTADGSWEPFASGKTAESGELHGLTTDEKFTEGVYRVELDTKSYWKALGISPFHEYAEVVFTANDSGHRHYTIAALLSPYSYSTTAVVSNPQN
120
P02767
28
147
81.6%
UniRef90_P02767
28
147
secondary structure
beta
32
38
secondary structure
beta
43
44
secondary structure
beta
50
55
secondary structure
beta
61
67
secondary structure
beta
74
75
secondary structure
beta
87
93
secondary structure
helix
95
102
secondary structure
beta
108
108
secondary structure
beta
111
117
secondary structure
beta
124
131
secondary structure
beta
135
140
secondary structure
beta
143
143
pfam
PF00576.18
Transthyretin
32
139
B
Transthyretin
Rattus norvegicus
SKCPLMVKVLDAVRGSPAVDVAVKVFKKTADGSWEPFASGKTAESGELHGLTTDEKFTEGVYRVELDTKSYWKALGISPFHEYAEVVFTANDSGHRHYTIAALLSPYSYSTTAVVSNPQN
120
P02767
28
147
81.6%
UniRef90_P02767
28
147
secondary structure
beta
32
34
secondary structure
beta
37
38
secondary structure
beta
43
44
secondary structure
beta
49
55
secondary structure
beta
61
68
secondary structure
beta
75
75
secondary structure
beta
87
93
secondary structure
helix
95
100
secondary structure
beta
108
117
secondary structure
beta
124
132
secondary structure
beta
135
139
secondary structure
beta
142
143
pfam
PF00576.18
Transthyretin
32
139
C
Transthyretin
Rattus norvegicus
SKCPLMVKVLDAVRGSPAVDVAVKVFKKTADGSWEPFASGKTAESGELHGLTTDEKFTEGVYRVELDTKSYWKALGISPFHEYAEVVFTANDSGHRHYTIAALLSPYSYSTTAVVSNPQN
120
P02767
28
147
81.6%
UniRef90_P02767
28
147
secondary structure
beta
32
38
secondary structure
beta
43
44
secondary structure
beta
49
55
secondary structure
beta
61
68
secondary structure
beta
87
93
secondary structure
helix
95
100
secondary structure
beta
108
108
secondary structure
beta
111
117
secondary structure
beta
124
132
secondary structure
beta
135
143
pfam
PF00576.18
Transthyretin
32
139
D
Transthyretin
Rattus norvegicus
SKCPLMVKVLDAVRGSPAVDVAVKVFKKTADGSWEPFASGKTAESGELHGLTTDEKFTEGVYRVELDTKSYWKALGISPFHEYAEVVFTANDSGHRHYTIAALLSPYSYSTTAVVSNPQN
120
P02767
28
147
81.6%
UniRef90_P02767
28
147
secondary structure
beta
32
38
secondary structure
beta
43
44
secondary structure
beta
49
55
secondary structure
beta
61
68
secondary structure
beta
88
93
secondary structure
helix
95
100
secondary structure
beta
108
108
secondary structure
beta
111
116
secondary structure
beta
125
132
secondary structure
beta
135
142
pfam
PF00576.18
Transthyretin
32
139
Transthyretin was shown in calorimetrics experiments to follow two-state folding/binding kinetics with the emergence of structure being linked to oligomerization (PMID:11152276).
1ie4
1kgi
1kgj
2qpf
MF4110002
Transthyretin (Sparus aurata)
1oo2
X-ray
1.56
homotetramer (dimer of dimers)
Sparus aurata
14644428
Folli C, Pasquato N, Ramazzina I, Battistutta R, Zanotti G, Berni R
Distinctive binding and structural properties of piscine transthyretin.
FEBS Lett.
2003
2
555
279-84
The thyroid hormone binding protein transthyretin (TTR) forms a macromolecular complex with the retinol-specific carrier retinol binding protein (RBP) in the blood of higher vertebrates. Piscine TTR is shown here to exhibit high binding affinity for L-thyroxine and negligible affinity for RBP. The 1.56 A resolution X-ray structure of sea bream TTR, compared with that of human TTR, reveals a high degree of conservation of the thyroid hormone binding sites. In contrast, some amino acid differences in discrete regions of sea bream TTR appear to be responsible for the lack of protein-protein recognition, providing evidence for the crucial role played by a limited number of residues in the interaction between RBP and TTR. Overall, this study makes it possible to draw conclusions on evolutionary relationships for RBPs and TTRs of phylogenetically distant vertebrates.
GO:0070324
thyroid hormone binding
GO:0070327
thyroid hormone transport
GO:0042572
retinol metabolic process
GO:0005576
extracellular region
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
1
Transthyretin-like folds
Transthyretin
A
Transthyretin (Precursor)
Sparus aurata
RCPLMVKILDAVKGTPAGSVALKVSQKTADGGWTQIATGVTDATGEIHNLITEQQFPAGVYRVEFDTKAYWTNQGSTPFHEVAEVVFDAHPEGHGHYTLALLLSPFSYTTTAVVSSVHE
119
Q9PTT3
33
148
76.8%
UniRef90_O93330
32
149
secondary structure
beta
36
42
secondary structure
beta
47
48
secondary structure
beta
53
59
secondary structure
beta
65
72
secondary structure
helix
85
87
secondary structure
beta
91
97
secondary structure
helix
99
105
secondary structure
beta
112
121
secondary structure
beta
129
136
secondary structure
beta
139
146
pfam
PF00576.18
Transthyretin
36
143
B
Transthyretin (Precursor)
Sparus aurata
RCPLMVKILDAVKGTPAGSVALKVSQKTADGGWTQIATGVTDATGEIHNLITEQQFPAGVYRVEFDTKAYWTNQGSTPFHEVAEVVFDAHPEGHGHYTLALLLSPFSYTTTAVVSSVHE
119
Q9PTT3
33
148
76.8%
UniRef90_O93330
32
149
secondary structure
beta
36
42
secondary structure
beta
47
48
secondary structure
beta
53
59
secondary structure
beta
65
72
secondary structure
helix
85
87
secondary structure
beta
91
97
secondary structure
helix
99
106
secondary structure
beta
112
121
secondary structure
beta
128
136
secondary structure
beta
139
147
pfam
PF00576.18
Transthyretin
36
143
C
Transthyretin (Precursor)
Sparus aurata
RCPLMVKILDAVKGTPAGSVALKVSQKTADGGWTQIATGVTDATGEIHNLITEQQFPAGVYRVEFDTKAYWTNQGSTPFHEVAEVVFDAHPEGHGHYTLALLLSPFSYTTTAVVSSVHE
119
Q9PTT3
33
148
76.8%
UniRef90_O93330
32
149
secondary structure
beta
36
42
secondary structure
beta
47
48
secondary structure
beta
53
59
secondary structure
beta
65
72
secondary structure
helix
85
87
secondary structure
beta
91
97
secondary structure
helix
99
106
secondary structure
beta
112
121
secondary structure
beta
128
136
secondary structure
beta
139
147
pfam
PF00576.18
Transthyretin
36
143
D
Transthyretin (Precursor)
Sparus aurata
RCPLMVKILDAVKGTPAGSVALKVSQKTADGGWTQIATGVTDATGEIHNLITEQQFPAGVYRVEFDTKAYWTNQGSTPFHEVAEVVFDAHPEGHGHYTLALLLSPFSYTTTAVVSSVHE
119
Q9PTT3
33
148
76.8%
UniRef90_O93330
32
149
secondary structure
beta
36
42
secondary structure
beta
47
48
secondary structure
beta
53
59
secondary structure
beta
65
72
secondary structure
helix
85
87
secondary structure
beta
91
97
secondary structure
helix
99
106
secondary structure
beta
112
121
secondary structure
beta
129
136
secondary structure
beta
139
146
pfam
PF00576.18
Transthyretin
36
143
Transthyretin was shown in calorimetrics experiments to follow two-state folding/binding kinetics with the emergence of structure being linked to oligomerization (PMID:11152276).
1sn0
1sn2
1sn5
MF4201001
Patj/Pals1 L27 domain complex (human/rat)
1y76
NMR
heterotetramer (dimer of dimers)
Mus musculus / Homo sapiens
15863617
Feng W, Long JF, Zhang M
A unified assembly mode revealed by the structures of tetrameric L27 domain complexes formed by mLin-2/mLin-7 and Patj/Pals1 scaffold proteins.
Proc. Natl. Acad. Sci. U.S.A.
2005
19
102
6861-6
Initially identified in Caenorhabditis elegans Lin-2 and Lin-7, L27 domain is a protein-protein interaction domain capable of organizing scaffold proteins into supramolecular assemblies by formation of heteromeric L27 domain complexes. L27 domain-mediated protein assemblies have been shown to play essential roles in cellular processes including asymmetric cell division, establishment and maintenance of cell polarity, and clustering of receptors and ion channels. The structural basis of L27 domain heteromeric complex assembly is controversial. We determined the high-resolution solution structure of the prototype L27 domain complex formed by mLin-2 and mLin-7 as well as the solution structure of the L27 domain complex formed by Patj and Pals1. The structures suggest that a tetrameric structure composed of two units of heterodimer is a general assembly mode for cognate pairs of L27 domains. Structural analysis of the L27 domain complex structures further showed that the central four-helix bundles mediating tetramer assembly are highly distinct between different pairs of L27 domain complexes. Biochemical studies revealed that the C-terminal alpha-helix responsible for the formation of the central helix bundle is a critical specificity determinant for each L27 domain in choosing its binding partner. Our results provide a unified picture for L27 domain-mediated protein-protein interactions.
GO:0005515
protein binding
GO:0070062
extracellular exosome
GO:0005737
cytoplasm
GO:0043234
protein complex
GO:0005923
bicellular tight junction
GO:0005886
plasma membrane
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
2
L27 domains
L27_2/N type
A
InaD-like protein
Mus musculus
NPAAEKMQVLQVLDRLRGKLQEKGDTTQNEKLSAFYETLKSPLFNQILTLQQSIKQLKGQLS
62
Q63ZW7
4
65
3.4%
UniRef90_Q63ZW7
4
65
secondary structure
helix
5
26
secondary structure
helix
32
43
secondary structure
helix
45
63
pfam
PF09045.7
L27_2
8
65
B
MAGUK p55 subfamily member 5
Homo sapiens
AVKILEIEDLFSSLKHIQHTLVDSQSQEDISLLLQLVQNKDFQNAFKIHNAITVHMNKAS
60
Q8N3R9
118
177
8.9%
UniRef90_Q9JLB2
118
177
secondary structure
helix
124
138
secondary structure
helix
142
155
secondary structure
helix
157
175
pfam
PF09060.7
L27_N
123
170
C
InaD-like protein
Mus musculus
NPAAEKMQVLQVLDRLRGKLQEKGDTTQNEKLSAFYETLKSPLFNQILTLQQSIKQLKGQLS
62
Q63ZW7
4
65
3.4%
UniRef90_Q63ZW7
4
65
secondary structure
helix
6
26
secondary structure
helix
32
43
secondary structure
helix
45
63
pfam
PF09045.7
L27_2
8
65
D
MAGUK p55 subfamily member 5
Homo sapiens
AVKILEIEDLFSSLKHIQHTLVDSQSQEDISLLLQLVQNKDFQNAFKIHNAITVHMNKAS
60
Q8N3R9
118
177
8.9%
UniRef90_Q9JLB2
118
177
secondary structure
helix
124
137
secondary structure
helix
142
155
secondary structure
helix
157
175
pfam
PF09060.7
L27_N
123
170
The interacting chains form a heterotetrameric L27 complex (PMID:15863617). L27 complexes formed by Lin-2 and Lin-7 proteins were shown to function as obligate heterodimers/tetramers undergoing a cooperative unfolding transition. Circular dichroism studies reveal that the individual monomers are largely unfolded outside the complex form (PMID:12110687).
MF4201002
Patj/Pals1 L27 domain complex (human/mouse)
1vf6
X-ray
2.10
heterotetramer (dimer of dimers)
Homo sapiens / Mus musculus
15241471
Li Y, Karnak D, Demeler B, Margolis B, Lavie A
Structural basis for L27 domain-mediated assembly of signaling and cell polarity complexes.
EMBO J.
2004
14
23
2723-33
L27 is a protein-binding domain that can assemble essential proteins for signaling and cell polarity into complexes by interacting in a heterodimeric manner. One of these protein complexes is the PATJ/PALS1/Crumbs tripartite complex, which is crucial for the establishment and maintenance of cell polarity. To reveal the structural basis underlining the obligate heterodimerization, we have determined the crystal structure of the PALS1-L27N/PATJ-L27 heterodimer complex. Each L27 domain is composed of three helices. The two L27 domains heterodimerize by building a compact structure consisting of a four-helix bundle formed by the first two helices of each L27 domain and one coiled-coil formed by the third helix of each domain. The large hydrophobic packing interactions contributed by all the helices of both L27 domains predominantly drive the heterodimer formation, which is likely to be a general feature of L27 domains. Combined with mutational studies, we can begin to understand the structural basis for the specificity of L27 binding pairs. Our results provide unique insights into L27 domain heterodimer complex, which is critical for cell polarization.
GO:0005515
protein binding
GO:0070830
bicellular tight junction assembly
GO:0070062
extracellular exosome
GO:0005737
cytoplasm
GO:0043234
protein complex
GO:0005923
bicellular tight junction
GO:0005886
plasma membrane
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
2
L27 domains
L27_2/N type
A
InaD-like protein
Homo sapiens
MKLQVLQVLDRLKMKLQEKGDTSQNEKLSMFYETLKSPLFNQILTLQQSIKQLKGQLNHILESGKETAAAKFERQHMDSSTSA
83
Q8NI35
9
67
3.3%
UniRef90_UPI0006B1AC65
9
82
secondary structure
helix
13
26
secondary structure
helix
32
43
secondary structure
helix
45
67
pfam
PF09045.7
L27_2
8
65
B
InaD-like protein
Homo sapiens
MKLQVLQVLDRLKMKLQEKGDTSQNEKLSMFYETLKSPLFNQILTLQQSIKQLKGQLNHILESGKETAAAKFERQHMDSSTSA
83
Q8NI35
9
67
3.3%
UniRef90_UPI0006B1AC65
9
82
secondary structure
helix
11
25
secondary structure
helix
32
43
secondary structure
helix
45
67
pfam
PF09045.7
L27_2
8
65
C
MAGUK p55 subfamily member 5
Mus musculus
MGSSHHHHHHSQDPDVEDLFSSLKHIQHTLVDSQSQEDISLLLQLVQNRDFQNAFKIHNAVTVHMSKASPPF
72
Q9JLB2
123
180
8.6%
UniRef90_Q9JLB2
123
180
secondary structure
helix
123
135
secondary structure
helix
141
155
secondary structure
helix
157
169
pfam
PF09060.7
L27_N
123
170
D
MAGUK p55 subfamily member 5
Mus musculus
MGSSHHHHHHSQDPDVEDLFSSLKHIQHTLVDSQSQEDISLLLQLVQNRDFQNAFKIHNAVTVHMSKASPPF
72
Q9JLB2
123
180
8.6%
UniRef90_Q9JLB2
123
180
secondary structure
helix
124
137
secondary structure
helix
141
155
secondary structure
helix
157
169
pfam
PF09060.7
L27_N
123
170
The interacting chains form a heterotetrameric L27 complex (PMID:15241471). L27 complexes formed by Lin-2 and Lin-7 proteins were shown to function as obligate heterodimers/tetramers undergoing a cooperative unfolding transition. Circular dichroism studies reveal that the individual monomers are largely unfolded outside the complex form (PMID:12110687).
MF4210002
L27 (Lin-2, Lin-7) domain complex (mouse)
1y74
NMR
heterotetramer (dimer of dimers)
Mus musculus
15863617
Feng W, Long JF, Zhang M
A unified assembly mode revealed by the structures of tetrameric L27 domain complexes formed by mLin-2/mLin-7 and Patj/Pals1 scaffold proteins.
Proc. Natl. Acad. Sci. U.S.A.
2005
19
102
6861-6
Initially identified in Caenorhabditis elegans Lin-2 and Lin-7, L27 domain is a protein-protein interaction domain capable of organizing scaffold proteins into supramolecular assemblies by formation of heteromeric L27 domain complexes. L27 domain-mediated protein assemblies have been shown to play essential roles in cellular processes including asymmetric cell division, establishment and maintenance of cell polarity, and clustering of receptors and ion channels. The structural basis of L27 domain heteromeric complex assembly is controversial. We determined the high-resolution solution structure of the prototype L27 domain complex formed by mLin-2 and mLin-7 as well as the solution structure of the L27 domain complex formed by Patj and Pals1. The structures suggest that a tetrameric structure composed of two units of heterodimer is a general assembly mode for cognate pairs of L27 domains. Structural analysis of the L27 domain complex structures further showed that the central four-helix bundles mediating tetramer assembly are highly distinct between different pairs of L27 domain complexes. Biochemical studies revealed that the C-terminal alpha-helix responsible for the formation of the central helix bundle is a critical specificity determinant for each L27 domain in choosing its binding partner. Our results provide a unified picture for L27 domain-mediated protein-protein interactions.
GO:0005515
protein binding
GO:0016323
basolateral plasma membrane
GO:0005911
cell-cell junction
GO:0045202
synapse
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
2
L27 domains
L27_1 type
A
Protein lin-7 homolog B
Mus musculus
LGLERDVSRAVELLERLQRSGELPPQKLQALQRVLQSRFCSAIREVYEQLYDTLDIT
57
O88951
8
64
27.5%
UniRef90_Q9Z252
8
64
secondary structure
helix
10
27
secondary structure
helix
32
43
secondary structure
helix
45
63
pfam
PF02828.13
L27
14
67
B
Peripheral plasma membrane protein CASK
Mus musculus
AVQRAKEVLEEISCYPENNDAKELKRILTQPHFMALLQTHDVVAHEVYSD
50
O70589
405
454
5.4%
UniRef90_O14936
405
454
secondary structure
helix
406
417
secondary structure
helix
423
433
secondary structure
helix
435
452
pfam
PF02828.13
L27
406
457
C
Protein lin-7 homolog B
Mus musculus
LGLERDVSRAVELLERLQRSGELPPQKLQALQRVLQSRFCSAIREVYEQLYDTLDIT
57
O88951
8
64
27.5%
UniRef90_Q9Z252
8
64
secondary structure
helix
10
27
secondary structure
helix
32
43
secondary structure
helix
45
63
pfam
PF02828.13
L27
14
67
D
Peripheral plasma membrane protein CASK
Mus musculus
AVQRAKEVLEEISCYPENNDAKELKRILTQPHFMALLQTHDVVAHEVYSD
50
O70589
405
454
5.4%
UniRef90_O14936
405
454
secondary structure
helix
406
417
secondary structure
helix
423
433
secondary structure
helix
435
451
pfam
PF02828.13
L27
406
457
The interacting chains form a heterotetrameric L27 complex (PMID:15863617). L27 complexes formed by Lin-2 and Lin-7 proteins were shown to function as obligate heterodimers/tetramers undergoing a cooperative unfolding transition. Circular dichroism studies reveal that the individual monomers are largely unfolded outside the complex form (PMID:12110687).
MF2201004
L27 (Lin-2, Lin-7) domain complex (human/C. elegans)
1zl8
NMR
heterodimer
Caenorhabditis elegans / Homo sapiens
16147993
Petrosky KY, Ou HD, Löhr F, Dötsch V, Lim WA
A general model for preferential hetero-oligomerization of LIN-2/7 domains: mechanism underlying directed assembly of supramolecular signaling complexes.
J. Biol. Chem.
2005
46
280
38528-36
LIN-2/7 (L27) domains are protein interaction modules that preferentially hetero-oligomerize, a property critical for their function in directing specific assembly of supramolecular signaling complexes at synapses and other polarized cell-cell junctions. We have solved the solution structure of the heterodimer composed of the L27 domains from LIN-2 and LIN-7. Comparison of this structure with other L27 domain structures has allowed us to formulate a general model for why most L27 domains form an obligate heterodimer complex. L27 domains can be divided in two types (A and B), with each heterodimer comprising an A/B pair. We have identified two keystone positions that play a central role in discrimination. The residues at these positions are energetically acceptable in the context of an A/B heterodimer, but would lead to packing defects or electrostatic repulsion in the context of A/A and B/B homodimers. As predicted by the model, mutations of keystone residues stabilize normally strongly disfavored homodimers. Thus, L27 domains are specifically optimized to avoid homodimeric interactions.
GO:0005515
protein binding
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
2
L27 domains
L27_1 type
A
LIN-7 (Fragment)
Caenorhabditis elegans
GSLNLERDVQRILELMEHVQKTGEVNNAKLASLQQVLQSEFFGAVREVYETVY
53
P90976
116
165
16.8%
UniRef90_Q9U245
8
57
secondary structure
helix
116
134
secondary structure
helix
139
149
secondary structure
helix
153
164
pfam
PF02828.13
L27
121
174
B
Peripheral plasma membrane protein CASK
Homo sapiens
SDAVQRAKEVLEEISCYPENNDAKELKRILTQPHFMALLQTHDVVAHEVYSDEA
54
O14936
403
456
5.8%
UniRef90_O14936
403
456
secondary structure
helix
404
416
secondary structure
helix
423
431
secondary structure
helix
437
450
pfam
PF02828.13
L27
406
457
The interacting chains form half of a heterotetrameric L27 complex (a dimer of dimers) (PMID:16147993). L27 complexes formed by Lin-2 and Lin-7 proteins were shown to function as obligate heterodimers/tetramers undergoing a cooperative unfolding transition. Circular dichroism studies reveal that the individual monomers are largely unfolded outside the complex form (PMID:12110687).
MF2140002
HPV E7 oncoprotein CR3 domain
2b9d
X-ray
1.60
homodimer
Human papillomavirus type 1a
16249186
Liu X, Clements A, Zhao K, Marmorstein R
Structure of the human Papillomavirus E7 oncoprotein and its mechanism for inactivation of the retinoblastoma tumor suppressor.
J. Biol. Chem.
2006
1
281
578-86
The E7 oncoprotein from human Papillomavirus (HPV) mediates cell transformation in part by binding to the human pRb tumor suppressor protein and E2F transcription factors, resulting in the dissociation of pRb from E2F transcription factors and the premature cell progression into the S-phase of the cell cycle. This activity is mediated by the LXCXE motif and the CR3 zinc binding domain of the E7 protein. In this study we report the x-ray crystal structure of the CR3 region of HPV E7 and a structure-based mutational analysis to investigate its mode of pRb and E2F binding and E2F displacement from pRb. The structure reveals a novel zinc-bound E7-CR3 obligate homodimer that contains two surface patches of sequence conservation. Mutation of residues within these patches reveals that one patch is required for pRb binding, whereas the other is required for E2F binding. We also show that both E7-mediated interactions are required to disrupt pRb.E2F complexes. Based on these studies we present a mechanistic model for how E7 displaces E2F from pRb. Because the CR3 region of HPV E7 has no detectable homology to other human proteins, the structure-function studies presented here provide an avenue for developing small molecule compounds that inhibit HPV-E7-mediated cell transformation.
GO:0003700
transcription factor activity, sequence-specific DNA binding
GO:0003677
DNA binding
GO:0046872
metal ion binding
GO:0019904
protein domain specific binding
GO:0006355
regulation of transcription, DNA-templated
GO:0006351
transcription, DNA-templated
GO:0039502
suppression by virus of host type I interferon-mediated signaling pathway
GO:0039645
modulation by virus of host G1/S transition checkpoint
GO:0030430
host cell cytoplasm
GO:0042025
host cell nucleus
Chain B was deleted. Chain C was generated from chain A using the biomatrix described in the original PDB file.
2
1
Other
Other
A
Protein E7
Human papillomavirus type 1a
MKQPYAVVASCAYCEKLVRLTVLADHSAIRQLEEMLLRSLNIVCPLCTLQRQ
52
P06465
42
93
55.9%
UniRef90_P06465
43
93
secondary structure
beta
44
51
secondary structure
beta
58
65
secondary structure
helix
67
79
secondary structure
beta
81
83
pfam
PF00527.15
E7
3
88
C
Protein E7
Human papillomavirus type 1a
MKQPYAVVASCAYCEKLVRLTVLADHSAIRQLEEMLLRSLNIVCPLCTLQRQ
52
P06465
42
93
55.9%
UniRef90_P06465
43
93
secondary structure
beta
44
51
secondary structure
beta
58
65
secondary structure
helix
67
79
secondary structure
beta
81
83
pfam
PF00527.15
E7
3
88
Evidence suggests that the E7-CR3 domain would not be able to maintain this tertiary structure in monomeric form or in the absence of zinc coordination and is, therefore, likely to be an obligate and zinc-dependent dimer (PMID:16249186). This is consistent with solution studies showing that HPV-E7 undergoes a monomer-dimer equilibrium with a dissociation constant of about 1 μm (PMID:11123931).
A
A close homologue sharing the same Pfam domain (PF00527.15) has been experimentally characterized as disordered in DisProt entry DP00024.
C
A close homologue sharing the same Pfam domain (PF00527.15) has been experimentally characterized as disordered in DisProt entry DP00024.
MF2110001
RhoA-binding domain in Rho-kinase
1uix
X-ray
1.80
homodimer
Bos taurus
12954645
Shimizu T, Ihara K, Maesaki R, Amano M, Kaibuchi K, Hakoshima T
Parallel coiled-coil association of the RhoA-binding domain in Rho-kinase.
J. Biol. Chem.
2003
46
278
46046-51
Rho-kinase is a serine/threonine protein kinase that regulates cytoskeletal events in cells. The enzyme activity of Rho-kinase is auto-inhibited in the free state but is activated through direct binding to the small GTPase Rho in the GTP-bound form. The crystal structure of the Rho-binding domain (RhoBD) of Rho-kinase has been determined at 1.8-A resolution by the multi-wavelength anomalous dispersion technique. The structure shows that RhoBD dimerizes to form a parallel coiled-coil with long consecutive alpha-helices extended to approximately 97 A and suggests that free Rho-kinase can also form a dimer through parallel self-association. At the middle region of the coiled-coil, the polypeptide chains are flexible and display loose "knobs-into-holes" packing of the side chains from both chains. RhoBD residues that have been shown to be critical for Rho-binding are spread in the positively charged C-terminal region. The parallel coiled-coil structure of our Rho-kinase RhoBD in the free form is different from the anti-parallel coiled-coil structure of RhoBD of protein kinase N when complexed with RhoA. Implications derived from these structural studies in relation to the mechanism of Rho-kinase activation will be addressed with previously reported experimental data.
GO:0005524
ATP binding
GO:0017048
Rho GTPase binding
GO:0046872
metal ion binding
GO:0004674
protein serine/threonine kinase activity
GO:0042752
regulation of circadian rhythm
GO:0048511
rhythmic process
GO:0006939
smooth muscle contraction
GO:0032956
regulation of actin cytoskeleton organization
GO:0006468
protein phosphorylation
GO:0007266
Rho protein signal transduction
GO:0030036
actin cytoskeleton organization
GO:0010825
positive regulation of centrosome duplication
GO:0005815
microtubule organizing center
GO:0005886
plasma membrane
GO:0005634
nucleus
GO:0005829
cytosol
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Coils and zippers
Coiled coil (dimeric)
A
Rho-associated protein kinase 2
Bos taurus
TSDVANLANEKEELNNKLKEAQEQLSRLKDEEISAAAIKAQFEKQLLTERTLKTQAVNKLAEIMNRKEP
69
Q28021
977
1047
5.1%
UniRef90_O75116
979
1047
secondary structure
helix
979
1041
secondary structure
helix
1043
1044
pfam
PF08912.8
Rho_Binding
978
1046
B
Rho-associated protein kinase 2
Bos taurus
GSTSDVANLANEKEELNNKLKEAQEQLSRLKDEEISAAAIKAQFEKQLLTERTLKTQAVNKLAEIMNRKEP
71
Q28021
977
1047
5.1%
UniRef90_O75116
979
1047
secondary structure
helix
979
1041
pfam
PF08912.8
Rho_Binding
978
1046
The subunits in the structure are bound via coiled coil interactions (PMID:12954645). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
MF2120008
Trp repressor protein (Escherichia coli)
3wrp
X-ray
1.80
homodimer
Escherichia coli
3375234
Lawson CL, Zhang RG, Schevitz RW, Otwinowski Z, Joachimiak A, Sigler PB
Flexibility of the DNA-binding domains of trp repressor.
Proteins
1988
1
3
18-31
An orthorhombic crystal form of trp repressor (aporepressor plus L-tryptophan ligand) was solved by molecular replacement, refined to 1.65 A resolution, and compared to the structure of the repressor in trigonal crystals. Even though these two crystal forms of repressor were grown under identical conditions, the refined structures have distinctly different conformations of the DNA-binding domains. Unlike the repressor/aporepressor structural transition, the conformational shift is not caused by the binding or loss of the L-tryptophan ligand. We conclude that while L-tryptophan binding is essential for forming a specific complex with trp operator DNA, the corepressor ligand does not lock the repressor into a single conformation that is complementary to the operator. This flexibility may be required by the various binding modes proposed for trp repressor in its search for and adherence to its three different operator sites.
GO:0043565
sequence-specific DNA binding
GO:0003700
transcription factor activity, sequence-specific DNA binding
GO:0045892
negative regulation of transcription, DNA-templated
GO:0006351
transcription, DNA-templated
GO:0005737
cytoplasm
Chain B was generated from chain A using the biomatrix described in the original PDB file.
2
1
Other
Trp repressor-like
A
Trp operon repressor
Escherichia coli
MAQQSPYSAAMAEQRHQEWLRFVDLLKNAYQNDLHLPLLNLMLTPDEREALGTRVRIVEELLRGEMSQRELKNELGAGIATITRGSNSLKAAPVELRQWLEEVLLKSD
108
P0A881
1
108
100%
UniRef90_A9MR96
1
106
secondary structure
helix
12
30
secondary structure
helix
35
42
secondary structure
helix
45
63
secondary structure
helix
68
75
secondary structure
helix
79
90
secondary structure
helix
94
104
pfam
PF01371.16
Trp_repressor
17
104
B
Trp operon repressor
Escherichia coli
MAQQSPYSAAMAEQRHQEWLRFVDLLKNAYQNDLHLPLLNLMLTPDEREALGTRVRIVEELLRGEMSQRELKNELGAGIATITRGSNSLKAAPVELRQWLEEVLLKSD
108
P0A881
1
108
100%
UniRef90_A9MR96
1
106
secondary structure
helix
12
30
secondary structure
helix
35
42
secondary structure
helix
45
63
secondary structure
helix
68
75
secondary structure
helix
79
90
secondary structure
helix
94
104
pfam
PF01371.16
Trp_repressor
17
104
The folding and dimerization of the Trp repressor were shown to be linked by both experimental (PMID:10329154, PMID:2223756, PMID:7578063) and computational studies (PMID:10465773).
1co0
1jhg
1rcs
1tro
1trr
1wrp
1wrs
1wrt
1zt9
2oz9
3ssw
3ssx
2xdi
MF2100003
Dimerization motif of Geminin
1uii
X-ray
2.00
homodimer
Homo sapiens
15260975
Saxena S, Yuan P, Dhar SK, Senga T, Takeda D, Robinson H, Kornbluth S, Swaminathan K, Dutta A
A dimerized coiled-coil domain and an adjoining part of geminin interact with two sites on Cdt1 for replication inhibition.
Mol. Cell
2004
2
15
245-58
Geminin is a cellular protein that associates with Cdt1 and inhibits Mcm2-7 loading during S phase. It prevents multiple cycles of replication per cell cycle and prevents episome replication. It also directly inhibits the HoxA11 transcription factor. Here we report that geminin forms a parallel coiled-coil homodimer with atypical residues in the dimer interface. Point mutations that disrupt the dimerization abolish interaction with Cdt1 and inhibition of replication. An array of glutamic acid residues on the coiled-coil domain surface interacts with positive charges in the middle of Cdt1. An adjoining region interacts independently with the N-terminal 100 residues of Cdt1. Both interactions are essential for replication inhibition. The negative residues on the coiled-coil domain and a different part of geminin are also required for interaction with HoxA11. Therefore a rigid cylinder with negative surface charges is a critical component of a bipartite interaction interface between geminin and its cellular targets.
GO:0042826
histone deacetylase binding
GO:0003714
transcription corepressor activity
GO:0070491
repressing transcription factor binding
GO:0007049
cell cycle
GO:0009887
organ morphogenesis
GO:0006461
protein complex assembly
GO:0045786
negative regulation of cell cycle
GO:0008156
negative regulation of DNA replication
GO:0045892
negative regulation of transcription, DNA-templated
GO:0005829
cytosol
GO:0005654
nucleoplasm
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Coils and zippers
Coiled coil (dimeric)
A
Geminin
Homo sapiens
PESSENKNLGGVTQESFDLMIKENPSSQYWKEVAEKRRKALYEALKENEKLHKEIEQKDNEIARLKKENKELAEVAEHVQYMA
83
O75496
70
152
39.7%
UniRef90_O75496
70
152
secondary structure
helix
94
151
pfam
PF07412.9
Geminin
1
184
B
Geminin
Homo sapiens
PESSENKNLGGVTQESFDLMIKENPSSQYWKEVAEKRRKALYEALKENEKLHKEIEQKDNEIARLKKENKELAEVAEHVQYMA
83
O75496
70
152
39.7%
UniRef90_O75496
70
152
secondary structure
helix
94
150
pfam
PF07412.9
Geminin
1
184
The subunits in the structure are bound via coiled coil interactions (PMID:15260975). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
1t6f
2wvr
MF2110002
GAL4 dimerization domain
1hbw
NMR
homodimer
Saccharomyces cerevisiae
11316794
Hidalgo P, Ansari AZ, Schmidt P, Hare B, Simkovich N, Farrell S, Shin EJ, Ptashne M, Wagner G
Recruitment of the transcriptional machinery through GAL11P: structure and interactions of the GAL4 dimerization domain.
Genes Dev.
2001
8
15
1007-20
The GAL4 dimerization domain (GAL4-dd) is a powerful transcriptional activator when tethered to DNA in a cell bearing a mutant of the GAL11 protein, named GAL11P. GAL11P (like GAL11) is a component of the RNA-polymerase II holoenzyme. Nuclear magnetic resonance (NMR) studies of GAL4-dd revealed an elongated dimer structure with C(2) symmetry containing three helices that mediate dimerization via coiled-coil contacts. The two loops between the three coiled coils form mobile bulges causing a variation of twist angles between the helix pairs. Chemical shift perturbation analysis mapped the GAL11P-binding site to the C-terminal helix alpha3 and the loop between alpha1 and alpha2. One GAL11P monomer binds to one GAL4-dd dimer rendering the dimer asymmetric and implying an extreme negative cooperativity mechanism. Alanine-scanning mutagenesis of GAL4-dd showed that the NMR-derived GAL11P-binding face is crucial for the novel transcriptional activating function of the GAL4-dd on GAL11P interaction. The binding of GAL4 to GAL11P, although an artificial interaction, represents a unique structural motif for an activating region capable of binding to a single target to effect gene expression.
GO:0000978
RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0001133
RNA polymerase II transcription factor activity, sequence-specific transcription regulatory region DNA binding
GO:0008270
zinc ion binding
GO:0001085
RNA polymerase II transcription factor binding
GO:0001077
transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0006012
galactose metabolic process
GO:0006366
transcription from RNA polymerase II promoter
GO:0000435
positive regulation of transcription from RNA polymerase II promoter by galactose
GO:0005634
nucleus
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Coils and zippers
Coiled coil (dimeric)
A
Regulatory protein GAL4
Saccharomyces cerevisiae
TRAHLTEVESRLERLEQLFLLIFPREDLDMILKMDSLRDIEALLTGLFVQDNVNKDA
57
P04386
50
106
6.5%
UniRef90_P04386
50
106
secondary structure
helix
55
67
secondary structure
helix
79
84
secondary structure
helix
87
96
pfam
PF03902.10
Gal4_dimer
50
106
B
Regulatory protein GAL4
Saccharomyces cerevisiae
TRAHLTEVESRLERLEQLFLLIFPREDLDMILKMDSLRDIEALLTGLFVQDNVNKDA
57
P04386
50
106
6.5%
UniRef90_P04386
50
106
secondary structure
helix
55
67
secondary structure
helix
79
84
secondary structure
helix
87
96
pfam
PF03902.10
Gal4_dimer
50
106
The subunits in the structure are bound via coiled coil interactions (PMID:11316794). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
3coq
MF2110003
Spindle pole body component SPC42
2q6q
X-ray
1.97
homodimer
Saccharomyces cerevisiae
18850724
Zizlsperger N, Malashkevich VN, Pillay S, Keating AE
Analysis of coiled-coil interactions between core proteins of the spindle pole body.
Biochemistry
2008
45
47
11858-68
The spindle pole body (SPB) is a multiprotein complex that organizes microtubules in yeast. Due to its large size and association with the nuclear membrane, little is known about its detailed structure. In particular, although many SPB components and some of the interactions between them have been identified, the molecular details of how most of these interactions occur are not known. The prevalence of predicted coiled-coil regions in SPB proteins suggests that some interactions may occur via coiled coils. Here this hypothesis is supported by biochemical characterization of isolated coiled-coil peptides derived from SPB proteins. Formation of four strongly self-associating coiled-coil complexes from Spc29, Spc42, and Spc72 was demonstrated by circular dichroism (CD) spectroscopy and a fluorescence resonance energy transfer (FRET) assay. Many weaker self- and heteroassociations were also detected by CD, FRET, and/or cross-linking. The thermal stabilities of nine candidate homooligomers were assessed; six unfolded cooperatively with melting temperatures ranging from <11 to >50 degrees C. Solution studies established that coiled-coil peptides derived from Spc42 and Spc72 form parallel dimers, and this was confirmed for Spc42 by a high-resolution crystal structure. These data contribute to a growing body of knowledge that will ultimately provide a detailed model of the SPB structure.
GO:0005200
structural constituent of cytoskeleton
GO:0005515
protein binding
GO:0007020
microtubule nucleation
GO:0030474
spindle pole body duplication
GO:0005823
central plaque of spindle pole body
GO:0005634
nucleus
GO:0005821
intermediate layer of spindle pole body
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Coils and zippers
Coiled coil (dimeric)
A
Spindle pole body component SPC42
Saccharomyces cerevisiae
AVQQNKELNFKLREKQNEIFELKKIAETLRSKLEKYVDITKKLEDQNLNLQIKISDLEKKLSDANSTFKEMRFP
74
P36094
65
138
20.4%
UniRef90_P36094
65
138
secondary structure
helix
68
124
pfam
PF11544.5
Spc42p
63
137
B
Spindle pole body component SPC42
Saccharomyces cerevisiae
AVQQNKELNFKLREKQNEIFELKKIAETLRSKLEKYVDITKKLEDQNLNLQIKISDLEKKLSDANSTFKEMRFP
74
P36094
65
138
20.4%
UniRef90_P36094
65
138
secondary structure
helix
68
126
pfam
PF11544.5
Spc42p
63
137
The subunits in the structure are bound via coiled coil interactions (PMID:18850724). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
MF2120009
Basic coiled-coil protein of unknown function (Eubacterium eligens ATCC 27750)
3hnw
X-ray
2.20
homodimer
Eubacterium eligens
Kim, Y., Cuff, M., Hendricks, R., Keigher, L., Joachimiak, A.
Crystal Structure of a Basic Coiled-Coil Protein of Unknown Function from Eubacterium eligens ATCC 27750
To be published
-
GO:0051301
cell division
GO:0007049
cell cycle
GO:0005737
cytoplasm
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Coils and zippers
Leucine zipper (dimeric)
A
Uncharacterized protein
Eubacterium eligens
SNAMSSKNTAEVILGGKVIKLGGYESEEYLQRVASYINNKITEFNKEESYRRMSAELRTDMMYLNIADDYFKAKKMADSLSLDIENKDKEIYDLKHELIAAQIKAESSAKEIKELKSEINKYQKNIVKLETELNDSKK
138
D0VWZ2
1
138
100%
UniRef90_D0VWZ2
1
138
secondary structure
beta
10
14
secondary structure
beta
17
21
secondary structure
helix
27
44
secondary structure
helix
48
51
secondary structure
helix
56
60
secondary structure
helix
63
75
secondary structure
helix
77
136
pfam
PF05164.10
ZapA
11
133
B
Uncharacterized protein
Eubacterium eligens
SNAMSSKNTAEVILGGKVIKLGGYESEEYLQRVASYINNKITEFNKEESYRRMSAELRTDMMYLNIADDYFKAKKMADSLSLDIENKDKEIYDLKHELIAAQIKAESSAKEIKELKSEINKYQKNIVKLETELNDSKK
138
D0VWZ2
1
138
100%
UniRef90_D0VWZ2
1
138
secondary structure
beta
11
14
secondary structure
beta
17
20
secondary structure
helix
27
45
secondary structure
helix
48
51
secondary structure
helix
56
60
secondary structure
helix
63
75
secondary structure
helix
77
136
pfam
PF05164.10
ZapA
11
133
The subunits in the structure are bound via coiled coil interactions. Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure. Leucine zippers, phenylalanine zippers and alanine zippers are subclasses of coiled coils where the hydrophobic interactions between subunits are predominantly formed by leucine, phenylalanine or alanine residues, respectively.
MF2200002
Geminin:Idas coiled coil dimer
4bry
X-ray
2.89
heterodimer
Homo sapiens
24064211
Caillat C, Pefani ED, Gillespie PJ, Taraviras S, Blow JJ, Lygerou Z, Perrakis A
The Geminin and Idas coiled coils preferentially form a heterodimer that inhibits Geminin function in DNA replication licensing.
J. Biol. Chem.
2013
Geminin is an important regulator of proliferation and differentiation in metazoans, which predominantly inhibits the DNA replication licensing factor Cdt1, preventing genome over-replication. We show that Geminin preferentially forms stable coiled-coil heterodimers with its homologue, Idas. In contrast to Idas:Geminin heterodimers, Idas homodimers are thermodynamically unstable and are unlikely to exist as a stable macromolecule under physiological conditions. The crystal structure of the homology regions of Idas in complex with Geminin showed a tight head-to-head heterodimeric coiled-coil. This Idas:Geminin heterodimer binds Cdt1 less strongly than Geminin:Geminin, still with high affinity (~30nM), but with notably different thermodynamic properties. Consistently, in Xenopus egg extracts, Idas:Geminin is less active in licensing inhibition compared to a Geminin:Geminin homodimer. In human cultured cells, ectopic expression of Idas leads to limited over-replication, which is counteracted by Geminin co-expression. The properties of the Idas:Geminin complex suggest it as the functional form of Idas, and provide a possible mechanism to modulate Geminin activity.
GO:0005515
protein binding
GO:0006275
regulation of DNA replication
GO:0007049
cell cycle
GO:0005634
nucleus
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
2
Coils and zippers
Coiled coil (dimeric)
A
Geminin
Homo sapiens
QESFDLMIKENPSSQYWKEVAEKRRKALYEALKENEKLHKEIEQKDNEIARLKKENKELAEVAEHVQYMAELIERLNG
78
O75496
83
160
37.3%
UniRef90_O75496
83
160
secondary structure
helix
94
157
pfam
PF07412.9
Geminin
1
184
B
Multicilin
Homo sapiens
PDVPPPEQYWKEVADQNQRALGDALVENNQLHVTLTQKQEEIASLKERNVQLKELASRTRHLASVLDKLMITQ
73
D6RGH6
173
245
19%
UniRef90_D6RGH6
179
245
secondary structure
helix
179
225
secondary structure
helix
227
241
pfam
PF07412.9
Geminin
174
257
The subunits in the structure are bound via coiled coil interactions (PMID:24064211). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
MF2110004
Coiled-coil trigger site of the rod domain of cortexillin I
1d7m
X-ray
2.70
homodimer
Dictyostelium discoideum
10745004
Burkhard P, Kammerer RA, Steinmetz MO, Bourenkov GP, Aebi U
The coiled-coil trigger site of the rod domain of cortexillin I unveils a distinct network of interhelical and intrahelical salt bridges.
Structure
2000
3
8
223-30
CONCLUSIONS: The knowledge gained from the structure could be used in the de novo design of alpha-helical coiled coils for applications such as two-stage drug targeting and delivery systems, and in the design of coiled coils as templates for combinatorial helical libraries in drug discovery and as synthetic carrier molecules. RESULTS: The X-ray crystal structure of the 18-heptad-repeat alpha-helical coiled-coil domain of the actin-bundling protein cortexillin I from Dictyostelium discoideum is a tightly packed parallel two-stranded alpha-helical coiled coil. It harbors a distinct 14-residue sequence motif that is essential for coiled-coil formation, and is a prerequisite for the assembly of cortexillin I. The atomic structure reveals novel types of ionic coiled-coil interactions. In particular, the structure shows that a characteristic interhelical and intrahelical salt-bridge pattern, in combination with the hydrophobic interactions occurring at the dimer interface, is the key structural feature of its coiled-coil trigger site. BACKGROUND: The parallel two-stranded alpha-helical coiled coil is the most frequently encountered subunit-oligomerization motif in proteins. The simplicity and regularity of this motif have made it an attractive system to explore some of the fundamental principles of protein folding and stability and to test the principles of de novo design.
GO:0051015
actin filament binding
GO:0042803
protein homodimerization activity
GO:0044351
macropinocytosis
GO:0043327
chemotaxis to cAMP
GO:0009617
response to bacterium
GO:0000916
actomyosin contractile ring contraction
GO:0036360
sorocarp stalk morphogenesis
GO:0051017
actin filament bundle assembly
GO:0045184
establishment of protein localization
GO:0036089
cleavage furrow formation
GO:0051495
positive regulation of cytoskeleton organization
GO:0001934
positive regulation of protein phosphorylation
GO:0034613
cellular protein localization
GO:0031152
aggregation involved in sorocarp development
GO:0019953
sexual reproduction
GO:0010628
positive regulation of gene expression
GO:0030866
cortical actin cytoskeleton organization
GO:0043520
regulation of myosin II filament assembly
GO:0003382
epithelial cell morphogenesis
GO:0043087
regulation of GTPase activity
GO:0051639
actin filament network formation
GO:0000281
mitotic cytokinesis
GO:0045180
basal cortex
GO:0005615
extracellular space
GO:0031255
lateral part of motile cell
GO:0032154
cleavage furrow
GO:0005826
actomyosin contractile ring
GO:0045335
phagocytic vesicle
GO:0031254
cell trailing edge
GO:0005886
plasma membrane
GO:0031252
cell leading edge
GO:0005829
cytosol
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Coils and zippers
Coiled coil (dimeric)
A
Cortexillin-1
Dictyostelium discoideum
EMANRLAGLENSLESEKVSREQLIKQKDQLNSLLASLESEGAEREKRLRELEAKLDETLKNLELEKLARMELEARLAKTEKDRAILELKLAEAIDEKSKLE
101
Q54HG2
243
343
22.7%
UniRef90_Q54HG2
243
343
secondary structure
helix
244
342
pfam
PF09304.7
Cortex-I_coil
231
337
B
Cortexillin-1
Dictyostelium discoideum
EMANRLAGLENSLESEKVSREQLIKQKDQLNSLLASLESEGAEREKRLRELEAKLDETLKNLELEKLARMELEARLAKTEKDRAILELKLAEAIDEKSKLE
101
Q54HG2
243
343
22.7%
UniRef90_Q54HG2
243
343
secondary structure
helix
244
342
pfam
PF09304.7
Cortex-I_coil
231
337
The subunits in the structure are bound via coiled coil interactions (PMID:10745004). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
MF2120010
Cell division factor ZapA
4p1m
X-ray
1.95
homodimer
Shigella sonnei
25002581
Roach EJ, Kimber MS, Khursigara CM
Crystal structure and site-directed mutational analysis reveals key residues involved in Escherichia coli ZapA function.
J. Biol. Chem.
2014
FtsZ is an essential cell division protein in Escherichia coli and its localization, filamentation and bundling at the mid-cell are required for Z-ring stability. Once assembled, the Z-ring recruits a series of proteins that comprise the bacterial divisome. FtsZ- associated proteins (Zaps) stabilize the Z-ring by increasing lateral interactions between individual filaments, bundling FtsZ to provide a scaffold for divisome assembly. The X-ray crystallographic structure of E. coli ZapA (EcZapA) was determined, identifying key structural differences from the existing ZapA structure from Pseudomonas aeruginosa, including a charged α-helix on the globular domains of the ZapA tetramer. Key helix residues in EcZapA were modified using site- directed mutagenesis. These ZapA variants significantly decreased FtsZ bundling in protein sedimentation assays when compared to wild-type (WT) ZapA proteins. Electron micrographs of ZapA-bundled FtsZ filaments showed the modified ZapA variants altered the number of FtsZ filaments per bundle. These in vitro results were corroborated in vivo by expressing the ZapA variants in an E. coli ∆zapA strain. In vivo, ZapA variants that altered FtsZ bundling showed an elongated phenotype, indicating improper cell division. Our findings highlight the importance of key ZapA residues that influence the extent of FtsZ bundling, and which ultimately affect Z-ring formation in dividing cells.
GO:0090529
cell septum assembly
GO:0005886
plasma membrane
GO:0005737
cytoplasm
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Coils and zippers
Coiled coil (dimeric)
A
Cell division protein ZapA
Shigella sonnei
MHHHHHHSIEGRSGMSAQPVDIQIFGRSLRVNCPPDQRDALNQAADDLNQRLQDLKERTRVTNTEQLVFIAALNISYELAQEKAKTRDYAASMEQRIRMLQQTIEQALLEQGRITEKTNQNFE
123
Q3YXW0
1
109
100%
UniRef90_A9MRG5
1
109
secondary structure
beta
5
10
secondary structure
beta
13
18
secondary structure
helix
21
45
secondary structure
helix
50
101
pfam
PF05164.10
ZapA
6
90
B
Cell division protein ZapA
Shigella sonnei
MHHHHHHSIEGRSGMSAQPVDIQIFGRSLRVNCPPDQRDALNQAADDLNQRLQDLKERTRVTNTEQLVFIAALNISYELAQEKAKTRDYAASMEQRIRMLQQTIEQALLEQGRITEKTNQNFE
123
Q3YXW0
1
109
100%
UniRef90_A9MRG5
1
109
secondary structure
beta
4
10
secondary structure
beta
13
19
secondary structure
helix
21
42
secondary structure
helix
50
101
pfam
PF05164.10
ZapA
6
90
The subunits in the structure are bound via coiled coil interactions (PMID:25002581). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
MF2120011
Cell division factor ZapB
2jee
X-ray
2.8
homodimer
Escherichia coli
18394147
Ebersbach G, Galli E, Møller-Jensen J, Löwe J, Gerdes K
Novel coiled-coil cell division factor ZapB stimulates Z ring assembly and cell division.
Mol. Microbiol.
2008
3
68
720-35
Formation of the Z ring is the first known event in bacterial cell division. However, it is not yet known how the assembly and contraction of the Z ring are regulated. Here, we identify a novel cell division factor ZapB in Escherichia coli that simultaneously stimulates Z ring assembly and cell division. Deletion of zapB resulted in delayed cell division and the formation of ectopic Z rings and spirals, whereas overexpression of ZapB resulted in nucleoid condensation and aberrant cell divisions. Localization of ZapB to the divisome depended on FtsZ but not FtsA, ZipA or FtsI, and ZapB interacted with FtsZ in a bacterial two-hybrid analysis. The simultaneous inactivation of FtsA and ZipA prevented Z ring assembly and ZapB localization. Time lapse microscopy showed that ZapB-GFP is present at mid-cell in a pattern very similar to that of FtsZ. Cells carrying a zapB deletion and the ftsZ84(ts) allele exhibited a synthetic sick phenotype and aberrant cell divisions. The crystal structure showed that ZapB exists as a dimer that is 100% coiled-coil. In vitro, ZapB self-assembled into long filaments and bundles. These results raise the possibility that ZapB stimulates Z ring formation directly via its capacity to self-assemble into larger structures.
GO:0042802
identical protein binding
GO:0043093
FtsZ-dependent cytokinesis
GO:0090529
cell septum assembly
GO:0005829
cytosol
GO:0032153
cell division site
Chains C and D were removed as chains A and B represent the biologically relevant dimer.
2
1
Coils and zippers
Coiled coil (dimeric)
A
Cell division protein ZapB
Escherichia coli
MTMSLEVFEKLEAKVQQAIDTITLLQMEIEELKEKNNSLSQEVQNAQHQREELERENNHLKEQQNGWQERLQALLGRMEEV
81
P0AF36
1
81
100%
UniRef90_A7ZUE3
1
81
secondary structure
helix
5
78
pfam
PF06005.9
DUF904
3
80
B
Cell division protein ZapB
Escherichia coli
MTMSLEVFEKLEAKVQQAIDTITLLQMEIEELKEKNNSLSQEVQNAQHQREELERENNHLKEQQNGWQERLQALLGRMEEV
81
P0AF36
1
81
100%
UniRef90_A7ZUE3
1
81
secondary structure
helix
5
45
secondary structure
helix
47
79
pfam
PF06005.9
DUF904
3
80
The subunits in the structure are bound via coiled coil interactions (PMID:18394147). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
MF2110005
Autophagy protein 16
3a7o
X-ray
2.50
homodimer
Saccharomyces cerevisiae
Fujioka, Y., Noda, N.N., Nakatogawa, H., Ohsumi, Y., Inagaki, F.
The dimeric coiled-coil structure of Atg16 and its functional significance in autophagy
To be published
-
GO:0042802
identical protein binding
GO:0030674
protein binding, bridging
GO:0034727
piecemeal microautophagy of nucleus
GO:0044805
late nucleophagy
GO:0000045
autophagosome assembly
GO:0006501
C-terminal protein lipidation
GO:0000422
mitophagy
GO:0032258
CVT pathway
GO:0000421
autophagosome membrane
GO:0034274
Atg12-Atg5-Atg16 complex
GO:0034045
pre-autophagosomal structure membrane
Chains C, D, E and F were removed as chains A and B represent the biologically relevant dimer.
2
1
Coils and zippers
Coiled coil (dimeric)
A
Autophagy protein 16
Saccharomyces cerevisiae
GSGAIGGNIVSHDDALLNTLAILQKELKSKEQEIRRLKEVIALKNKNTERLNDELISGTIENNVLQQKLSDLKKE
75
Q03818
49
123
50%
UniRef90_A6ZML8
50
123
secondary structure
helix
61
117
pfam
PF08614.8
ATG16
61
143
B
Autophagy protein 16
Saccharomyces cerevisiae
GSGAIGGNIVSHDDALLNTLAILQKELKSKEQEIRRLKEVIALKNKNTERLNDELISGTIENNVLQQKLSDLKKE
75
Q03818
49
123
50%
UniRef90_A6ZML8
50
123
secondary structure
helix
62
112
pfam
PF08614.8
ATG16
61
143
The subunits in the structure are bound via coiled coil interactions. Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
3a7p
MF3110001
Assembly domain of cartilage oligomeric matrix protein (chicken)
1aq5
NMR
homotrimer
Gallus gallus
9699631
Dames SA, Kammerer RA, Wiltscheck R, Engel J, Alexandrescu AT
NMR structure of a parallel homotrimeric coiled coil.
Nat. Struct. Biol.
1998
8
5
687-91
The solution structure of the oligomerization domain of cartilage matrix protein (also known as matrilin-1) has been determined by heteronuclear NMR spectroscopy. The domain folds into a parallel, disulfide-linked, three-stranded, alpha-helical coiled coil, spanning five heptad repeats in the amino acid sequence. The sequence of the first two heptad repeats shows some deviations from the consensus of hydrophobic and hydrophilic residue preferences. While the corresponding region of the coiled coil has a higher intrinsic flexibility, backbone alpha-helix and superhelix parameters are consistent with a regular coiled coil structure.
GO:0005201
extracellular matrix structural constituent
GO:0005509
calcium ion binding
GO:0005578
proteinaceous extracellular matrix
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
3
1
Coils and zippers
Coiled coil (trimeric)
A
Cartilage matrix protein
Gallus gallus
GSHMEEDPCECKSIVKFQTKVEELINTLQQKLEAVAKRIEALENKII
47
P05099
447
493
9.5%
UniRef90_P05099
450
493
secondary structure
helix
459
492
pfam
PF10393.6
Matrilin_ccoil
448
492
B
Cartilage matrix protein
Gallus gallus
GSHMEEDPCECKSIVKFQTKVEELINTLQQKLEAVAKRIEALENKII
47
P05099
447
493
9.5%
UniRef90_P05099
450
493
secondary structure
helix
459
492
pfam
PF10393.6
Matrilin_ccoil
448
492
C
Cartilage matrix protein
Gallus gallus
GSHMEEDPCECKSIVKFQTKVEELINTLQQKLEAVAKRIEALENKII
47
P05099
447
493
9.5%
UniRef90_P05099
450
493
secondary structure
helix
459
492
pfam
PF10393.6
Matrilin_ccoil
448
492
The subunits in the structure are bound via coiled coil interactions (PMID:9699631). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
MF3140001
Bacteriophage T4 fibritin
1aa0
X-ray
2.20
homotrimer
Enterobacteria phage T4
9261070
Tao Y, Strelkov SV, Mesyanzhinov VV, Rossmann MG
Structure of bacteriophage T4 fibritin: a segmented coiled coil and the role of the C-terminal domain.
Structure
1997
6
5
789-98
CONCLUSIONS: The residues within the C-terminal domain make extensive hydrophobic and some polar intersubunit interactions. This is consistent with the C-terminal domain being important for the correct assembly of fibritin, as shown earlier by mutational studies. Tight interactions between the C-terminal residues of adjacent subunits counteract the latent instability that is suggested by the structural properties of the coiled-coil segments. Trimerization is likely to begin with the formation of the C-terminal domain which subsequently initiates the assembly of the coiled coil. The interplay between the stabilizing effect of the C-terminal domain and the labile coiled-coil domain may be essential for the fibritin function and for the correct functioning of many other alpha-fibrous proteins. RESULTS: The three-dimensional structure of fibritin E, a deletion mutant of wild-type fibritin, was determined to 2.2 A resolution by X-ray crystallography. Three identical subunits of 119 amino acid residues form a trimeric parallel coiled-coil domain and a small globular C-terminal domain about a crystallographic threefold axis. The coiled-coil domain is divided into three segments that are separated by insertion loops. The C-terminal domain, which consists of 30 residues from each subunit, contains a beta-propeller-like structure with a hydrophobic interior. BACKGROUND: Oligomeric coiled-coil motifs are found in numerous protein structures; among them is fibritin, a structural protein of bacteriophage T4, which belongs to a class of chaperones that catalyze a specific phage-assembly process. Fibritin promotes the assembly of the long tail fibers and their subsequent attachment to the tail baseplate; it is also a sensing device that controls the retraction of the long tail fibers in adverse environments and, thus, prevents infection. The structure of fibritin had been predicted from sequence and biochemical analyses to be mainly a triple-helical coiled coil. The determination of its structure at atomic resolution was expected to give insights into the assembly process and biological function of fibritin, and the properties of modified coiled-coil structures in general.
GO:0019012
virion
Chains B and C were generated from chain A using the biomatrices described in the original PDB file.
3
1
Other
Coiled coil/foldon domain
A
Fibritin
Enterobacteria phage T4
VSGLNNAVQNLQVEIGNNSAGIKGQVVALNTLVNGTNPNGSTVEERGLTNSIKANETNIASVTQEVNTAKGNISSLQGDVQALQEAGYIPEAPRDGQAYVRKDGEWVLLSTFL
113
P10104
372
484
23.2%
UniRef90_P10104
372
484
secondary structure
helix
373
386
secondary structure
helix
393
405
secondary structure
helix
414
417
secondary structure
helix
419
455
secondary structure
beta
459
459
secondary structure
beta
461
461
secondary structure
beta
470
473
secondary structure
beta
476
479
secondary structure
helix
480
482
pfam
PF07921.9
Fibritin_C
372
483
B
Fibritin
Enterobacteria phage T4
VSGLNNAVQNLQVEIGNNSAGIKGQVVALNTLVNGTNPNGSTVEERGLTNSIKANETNIASVTQEVNTAKGNISSLQGDVQALQEAGYIPEAPRDGQAYVRKDGEWVLLSTFL
113
P10104
372
484
23.2%
UniRef90_P10104
372
484
secondary structure
helix
373
386
secondary structure
helix
393
405
secondary structure
helix
414
417
secondary structure
helix
419
455
secondary structure
beta
459
459
secondary structure
beta
461
461
secondary structure
beta
470
473
secondary structure
beta
476
479
secondary structure
helix
480
482
pfam
PF07921.9
Fibritin_C
372
483
C
Fibritin
Enterobacteria phage T4
VSGLNNAVQNLQVEIGNNSAGIKGQVVALNTLVNGTNPNGSTVEERGLTNSIKANETNIASVTQEVNTAKGNISSLQGDVQALQEAGYIPEAPRDGQAYVRKDGEWVLLSTFL
113
P10104
372
484
23.2%
UniRef90_P10104
372
484
secondary structure
helix
373
386
secondary structure
helix
393
405
secondary structure
helix
414
417
secondary structure
helix
419
455
secondary structure
beta
459
459
secondary structure
beta
461
461
secondary structure
beta
470
473
secondary structure
beta
476
479
secondary structure
helix
480
482
pfam
PF07921.9
Fibritin_C
372
483
The foldon domain folds into a trimeric beta-propeller structure and undergoes a two-state unfolding transition from folded trimer to unfolded monomers (PMID:15033360). The other subunits in the structure are bound via coiled coil interactions (PMID:9261070). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
1avy
2bsg
3j2o
2ww6
2ww7
4ncu
4ncv
4ncw
1v1h
1v1i
2kbl
3a1m
1u0p
MF3100001
Trimerization domain from lung surfactant protein D
1m7l
NMR
homotrimer
Homo sapiens
12495025
Kovacs H, O'Ddonoghue SI, Hoppe HJ, Comfort D, Reid KB, Campbell D, Nilges M
Solution structure of the coiled-coil trimerization domain from lung surfactant protein D.
J. Biomol. NMR
2002
2
24
89-102
Surfactant protein D (SP-D) is one of four known protein components of the pulmonary surfactant lining the lung alveoli. It is involved in immune and allergic responses. SP-D occurs as a tetramer of trimers. Trimerization is thought to be initiated by a coiled coil domain. We have determined the solution structure of a 64-residue peptide encompassing the coiled coil domain of human SP-D. As predicted, the domain forms a triple-helical parallel coiled coil. As with all symmetric oligomers, the structure calculation was complicated by the symmetry degeneracy in the NMR spectra. We used the symmetry-ADR (ambiguous distance restraint) structure calculation method to solve the structure. The results demonstrate that the leucine zipper region of SP-D is an autonomously folded domain. The structure is very similar to the independently determined X-ray crystal structure, differing mainly at a single residue, Tyr248. This residue is completely symmetric in the solution structure, and markedly asymmetric in the crystalline phase. This difference may be functionally important, as it affects the orientation of the antigenic surface presented by SP-D.
GO:0030246
carbohydrate binding
GO:0005515
protein binding
GO:0050766
positive regulation of phagocytosis
GO:0044267
cellular protein metabolic process
GO:0045087
innate immune response
GO:0072593
reactive oxygen species metabolic process
GO:0045085
negative regulation of interleukin-2 biosynthetic process
GO:0050776
regulation of immune response
GO:0048286
lung alveolus development
GO:0048246
macrophage chemotaxis
GO:0042742
defense response to bacterium
GO:0042130
negative regulation of T cell proliferation
GO:0006898
receptor-mediated endocytosis
GO:0007585
respiratory gaseous exchange
GO:0043129
surfactant homeostasis
GO:0005581
collagen trimer
GO:0005764
lysosome
GO:0005789
endoplasmic reticulum membrane
GO:0045334
clathrin-coated endocytic vesicle
GO:0042599
lamellar body
GO:0005578
proteinaceous extracellular matrix
GO:0005615
extracellular space
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
3
1
Coils and zippers
Coiled coil (trimeric)
A
Pulmonary surfactant-associated protein D
Homo sapiens
GLPDVASLRQQVEALQGQVQHLQAAFSQYKKVELFPNGGI
40
P35247
220
259
10.7%
UniRef90_P35247
220
257
secondary structure
helix
221
249
pfam
PF09006.8
Surfac_D-trimer
224
269
B
Pulmonary surfactant-associated protein D
Homo sapiens
GLPDVASLRQQVEALQGQVQHLQAAFSQYKKVELFPNGGI
40
P35247
220
259
10.7%
UniRef90_P35247
220
257
secondary structure
helix
221
249
pfam
PF09006.8
Surfac_D-trimer
224
269
C
Pulmonary surfactant-associated protein D
Homo sapiens
GLPDVASLRQQVEALQGQVQHLQAAFSQYKKVELFPNGGI
40
P35247
220
259
10.7%
UniRef90_P35247
220
257
secondary structure
helix
221
249
pfam
PF09006.8
Surfac_D-trimer
224
269
The subunits in the structure are bound via coiled coil interactions (PMID:12495025). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
1b08
1pw9
1pwb
2ggu
2ggx
2orj
2ork
2os9
2ria
2rib
2ric
2rid
2rie
3dbz
3g81
3g83
3g84
3ikn
3ikp
3ikq
3ikr
4e52
4m17
4m18
MF3120001
Major outer membrane lipoprotein
1jcc
X-ray
1.70
homotrimer
Shigella flexneri
12741822
Liu J, Dai J, Lu M
Zinc-mediated helix capping in a triple-helical protein.
Biochemistry
2003
19
42
5657-64
Specific sequence signals at alpha-helix termini can assist protein folding by punctuating and cueing secondary structural elements in the final native conformation. Here we report the crystallization of a 56-residue alanine-containing peptide, denoted Ala-10(56), in the presence of Zn(2+). The 1.7 A crystal structure shows that Ala-10(56) forms a parallel trimeric coiled coil with three zinc ions anchoring distinct capping conformations at the amino-terminal ends of the three helices. In each polypeptide chain, the free alpha-amino nitrogen and carbonyl oxygen of the amino-terminal Ser residue coordinate to a Zn(2+) ion to form a five-membered chelate, and the syn-unidentate interaction of the Asp7 side chain with the Zn(2+) cation leads to the formation of a unique docking arrangement for helix capping. Moreover, the coordination of the zinc ion involves a neighboring trimer molecule in the crystal. Consequently, the crystal contacts are stabilized by carboxylate-Zn(2+) interactions between four Ala-10(56) trimers in the crystal lattice. The observed synergy between the protein-zinc ion recognition and the helix-packing arrangements would contribute to the conformational specificity of the Ala-10(56) trimer.
GO:0009279
cell outer membrane
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
3
1
Coils and zippers
Alanine zipper (trimeric)
A
Major outer membrane lipoprotein
Shigella flexneri
SSNAKIDQLSSDAQTANAKADQASNDANAARSDAQAAKDDAARANQRLDNMATKYR
56
P69780
22
77
71.8%
UniRef90_P69778
22
77
secondary structure
helix
25
70
pfam
PF04728.10
LPP
26
78
B
Major outer membrane lipoprotein
Shigella flexneri
SSNAKIDQLSSDAQTANAKADQASNDANAARSDAQAAKDDAARANQRLDNMATKYR
56
P69780
22
77
71.8%
UniRef90_P69778
22
77
secondary structure
helix
25
71
pfam
PF04728.10
LPP
26
78
C
Major outer membrane lipoprotein
Shigella flexneri
SSNAKIDQLSSDAQTANAKADQASNDANAARSDAQAAKDDAARANQRLDNMATKYR
56
P69780
22
77
71.8%
UniRef90_P69778
22
77
secondary structure
helix
25
70
pfam
PF04728.10
LPP
26
78
The subunits in the structure are bound via coiled coil interactions (PMID:12741822). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure. Leucine zippers, phenylalanine zippers and alanine zippers are subclasses of coiled coils where the hydrophobic interactions between subunits are predominantly formed by leucine, phenylalanine or alanine residues, respectively.
1eq7
1kfm
1kfn
1jcd
1t8z
2gus
2guv
MF3120002
DUF16 domain of MPN010 (Mycoplasma pneumoniae)
2ba2
X-ray
1.80
homotrimer
Mycoplasma pneumoniae
16522803
Shin DH, Kim JS, Yokota H, Kim R, Kim SH
Crystal structure of the DUF16 domain of MPN010 from Mycoplasma pneumoniae.
Protein Sci.
2006
4
15
921-8
We have determined the crystal structure of the DUF16 domain of unknown function encoded by the gene MPN010 of Mycoplasma pneumoniae at 1.8 A resolution. The crystal structure revealed that this domain is composed of two separated homotrimeric coiled-coils. The shorter one consists of 11 highly conserved residues. The sequence comprises noncanonical heptad repeats that induce a right-handed coiled-coil structure. The longer one is composed of approximately nine heptad repeats. In this coiled-coil structure, there are three distinguishable regions that confer unique structural properties compared with other known homotrimeric coiled-coils. The first part, containing one stutter, is an unusual phenylalanine-rich region that is not found in any other coiled-coil structures. The second part is a highly conserved glutamine-rich region, frequently found in other trimeric coiled-coil structures. The last part is composed of prototype heptad repeats. The phylogenetic analysis of the DUF16 family together with a secondary structure prediction shows that the DUF16 family can be classified into five subclasses according to N-terminal sequences. Based on the structural comparison with other coiled-coil structures, a probable molecular function of the DUF16 family is discussed.
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
3
1
Coils and zippers
Coiled coil (trimeric)
A
UPF0134 protein MPN_010
Mycoplasma pneumoniae
VKTPGTRYVTHKQLDEKLKNFVTKTEFKEFQTVVMESFAVQNQNIDAQGEQIKELQVEQKAQGKTLQLILEALQGINKRLDNLES
85
P75103
46
130
64.9%
UniRef90_P75103
46
130
secondary structure
beta
53
53
secondary structure
beta
55
55
secondary structure
helix
56
63
secondary structure
beta
66
66
secondary structure
beta
68
68
secondary structure
helix
69
128
pfam
PF01519.13
DUF16
37
130
B
UPF0134 protein MPN_010
Mycoplasma pneumoniae
VKTPGTRYVTHKQLDEKLKNFVTKTEFKEFQTVVMESFAVQNQNIDAQGEQIKELQVEQKAQGKTLQLILEALQGINKRLDNLES
85
P75103
46
130
64.9%
UniRef90_P75103
46
130
secondary structure
beta
53
53
secondary structure
beta
55
55
secondary structure
helix
56
63
secondary structure
beta
66
66
secondary structure
beta
68
68
secondary structure
helix
69
129
pfam
PF01519.13
DUF16
37
130
C
UPF0134 protein MPN_010
Mycoplasma pneumoniae
VKTPGTRYVTHKQLDEKLKNFVTKTEFKEFQTVVMESFAVQNQNIDAQGEQIKELQVEQKAQGKTLQLILEALQGINKRLDNLES
85
P75103
46
130
64.9%
UniRef90_P75103
46
130
secondary structure
beta
53
53
secondary structure
beta
55
55
secondary structure
helix
56
63
secondary structure
beta
66
66
secondary structure
beta
68
68
secondary structure
helix
69
128
pfam
PF01519.13
DUF16
37
130
The subunits in the structure are bound via coiled coil interactions (PMID:16522803). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
MF3100002
Dystrophia myotonin-protein kinase coiled-coil domain
1wt6
X-ray
1.60
homotrimer
Homo sapiens
16770013
Garcia P, Ucurum Z, Bucher R, Svergun DI, Huber T, Lustig A, Konarev PV, Marino M, Mayans O
Molecular insights into the self-assembly mechanism of dystrophia myotonica kinase.
FASEB J.
2006
8
20
1142-51
Self-assembly via coiled-coil domains (CC) is crucial for the regulation of the dystrophia myotonica kinase (DMPK) -related family of kinases. These CC domains are thought to form dimeric arrangements and thus to mediate dimerization in these enzymes. Using size exclusion chromatography combined with multiangle static light scattering, we analyzed the oligomeric state of DMPK as well as that of a truncated variant lacking the CC fraction. Remarkably, both forms were found to assemble into robust dimers. In contrast, the CC domain in isolation yielded trimeric assemblies, indicating that the oligomerization properties of CC domains from this kinase family are more diversified than anticipated. The crystal structure of this CC has been elucidated to 1.6 angstroms resolution and its properties in solution established using sedimentation equilibrium and thermal denaturation. These data show that, contrary to expectations, the self-assembly of DMPK is not dictated by the association properties of its CC domain. Instead, it appears to be driven by sequence segments flanking both N and C termini of the catalytic kinase fraction, as suggested by models of head-to-head dimers based on small angle X-ray scattering data. Our findings support a shared pattern of assembly across DMPK, ROCKs, and MRCK members of this family.
GO:0017020
myosin phosphatase regulator activity
GO:0004674
protein serine/threonine kinase activity
GO:0046872
metal ion binding
GO:0031072
heat shock protein binding
GO:0005524
ATP binding
GO:0051823
regulation of synapse structural plasticity
GO:0010657
muscle cell apoptotic process
GO:0006874
cellular calcium ion homeostasis
GO:0014722
regulation of skeletal muscle contraction by calcium ion signaling
GO:0014853
regulation of excitatory postsynaptic membrane potential involved in skeletal muscle contraction
GO:0050790
regulation of catalytic activity
GO:0010830
regulation of myotube differentiation
GO:0018105
peptidyl-serine phosphorylation
GO:1903779
regulation of cardiac conduction
GO:0002028
regulation of sodium ion transport
GO:0006998
nuclear envelope organization
GO:0005829
cytosol
GO:0033017
sarcoplasmic reticulum membrane
GO:0005886
plasma membrane
GO:0031307
integral component of mitochondrial outer membrane
GO:0005640
nuclear outer membrane
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
3
1
Coils and zippers
Coiled coil (trimeric)
A
Myotonin-protein kinase
Homo sapiens
GAMAEAEAEVTLRELQEALEEEVLTRQSLSREMEAIRTDNQNFASQLREAEARNRDLEAHVRQLQERMELLQAEGATAVTG
81
Q09013
457
537
12.9%
UniRef90_Q09013
467
537
secondary structure
helix
468
528
pfam
PF08826.7
DMPK_coil
470
530
B
Myotonin-protein kinase
Homo sapiens
GAMAEAEAEVTLRELQEALEEEVLTRQSLSREMEAIRTDNQNFASQLREAEARNRDLEAHVRQLQERMELLQAEGATAVTG
81
Q09013
457
537
12.9%
UniRef90_Q09013
467
537
secondary structure
helix
467
526
pfam
PF08826.7
DMPK_coil
470
530
D
Myotonin-protein kinase
Homo sapiens
GAMAEAEAEVTLRELQEALEEEVLTRQSLSREMEAIRTDNQNFASQLREAEARNRDLEAHVRQLQERMELLQAEGATAVTG
81
Q09013
457
537
12.9%
UniRef90_Q09013
467
537
secondary structure
helix
468
526
pfam
PF08826.7
DMPK_coil
470
530
The subunits in the structure are bound via coiled coil interactions (PMID:16770013). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
MF2140003
Gene V protein
1gvp
X-ray
1.60
homodimer
Enterobacteria phage f1
9098886
Su S, Gao YG, Zhang H, Terwilliger TC, Wang AH
Analyses of the stability and function of three surface mutants (R82C, K69H, and L32R) of the gene V protein from Ff phage by X-ray crystallography.
Protein Sci.
1997
4
6
771-80
The high-resolution crystal structure of the gene V protein (GVP) from the Ff filamentous phages (M13, fl, fd) has been solved recently for the wild-type and two surface mutant (Y41F and Y41H) proteins, leading to a plausible model for the polymeric GVP-ssDNA complex (Guan Y, Zhang H, Wang AHJ, 1995, Protein Sci 4:187-197). The model of the complex shows extensive contacts between neighboring dimer GVPs involving electrostatic interactions between the K69 from one and the D79 and R82 from the next dimer. In addition, hydrophobic interactions between the amino acids L32 and L44 from one and G23 from the next dimer also contribute to the dimer-dimer interactions. Mutations at the L32, K69, and R82 amino acid sites generally destabilize the protein and many of these affect the function of the phage. We have studied the structural effects of three mutant proteins involving those sites, i.e., L32R, K69H, and R82C, by X-ray crystallographic analysis at 2.0 A resolution. In L32R GVP, the structural perturbation is localized, whereas in K69H and R82C GVPs, some long-range effects are also detected in addition to the local perturbation. We have interpreted the protein stability and the functional properties associated with those mutations in terms of the observed structural perturbations.
GO:0003697
single-stranded DNA binding
GO:0039684
rolling circle single-stranded viral DNA replication
Chain B was generated from chain A using the biomatrices described in the original PDB file.
2
1
Other
Other
A
DNA-Binding protein G5P
Enterobacteria phage f1
MIKVEIKPSQAQFTTRSGVSRQGKPYSLNEQLCYVDLGNEYPVLVKITLDEGQPAYAPGLYTVHLSSFKVGQFGSLMIDRLRLVPAK
87
P69543
1
87
100%
UniRef90_P69543
1
87
secondary structure
beta
4
6
secondary structure
helix
8
10
secondary structure
beta
14
19
secondary structure
beta
25
35
secondary structure
beta
43
48
secondary structure
beta
59
63
secondary structure
helix
65
67
secondary structure
beta
68
70
secondary structure
beta
76
78
secondary structure
beta
83
85
pfam
PF02303.14
Phage_DNA_bind
2
83
B
DNA-Binding protein G5P
Enterobacteria phage f1
MIKVEIKPSQAQFTTRSGVSRQGKPYSLNEQLCYVDLGNEYPVLVKITLDEGQPAYAPGLYTVHLSSFKVGQFGSLMIDRLRLVPAK
87
P69543
1
87
100%
UniRef90_P69543
1
87
secondary structure
beta
4
6
secondary structure
helix
8
10
secondary structure
beta
14
19
secondary structure
beta
25
35
secondary structure
beta
43
48
secondary structure
beta
59
63
secondary structure
helix
65
67
secondary structure
beta
68
70
secondary structure
beta
76
78
secondary structure
beta
83
85
pfam
PF02303.14
Phage_DNA_bind
2
83
Reversible denaturation experiments have shown that the dimeric gene V protein unfolds in a single cooperative transition from a folded dimer into two unfolded monomers (PMID:2007116).
1ae2
1ae3
1gkh
2gn5
2gva
2gvb
1vqa
1vqb
1vqc
1vqd
1vqe
1vqf
1vqg
1vqh
1vqi
1vqj
1yha
1yhb
MF2140004
Bacteriophage f29 scaffolding protein gp7
1no4
X-ray
2.20
homodimer
Bacillus phage phi29
12778115
Morais MC, Kanamaru S, Badasso MO, Koti JS, Owen BA, McMurray CT, Anderson DL, Rossmann MG
Bacteriophage phi29 scaffolding protein gp7 before and after prohead assembly.
Nat. Struct. Biol.
2003
7
10
572-6
Three-dimensional structures of the double-stranded DNA bacteriophage phi29 scaffolding protein (gp7) before and after prohead assembly have been determined at resolutions of 2.2 and 2.8 A, respectively. Both structures are dimers that resemble arrows, with a four-helix bundle composing the arrowhead and a coiled coil forming the tail. The structural resemblance of gp7 to the yeast transcription factor GCN4 suggests a DNA-binding function that was confirmed by native gel electrophoresis. DNA binding to gp7 may have a role in mediating the structural transition from prohead to mature virus and scaffold release. A cryo-EM analysis indicates that gp7 is arranged inside the capsid as a series of concentric shells. The position of the higher density features in these shells correlates with the positions of hexamers in the equatorial region of the capsid, suggesting that gp7 may regulate formation of the prolate head through interactions with these hexamers.
GO:0003677
DNA binding
GO:0019076
viral release from host cell
GO:0046806
viral scaffold
Chains C and D were removed as chains A and B represent the biologically relevant dimer.
2
1
Coils and zippers
Coiled coil (dimeric)
A
Head morphogenesis protein
Bacillus phage phi29
PLKPEEHEDILNKLLDPELAQSERTEALQQLRVNYGSFVSEYNDLTKSHEKLAAEKDDLIVSNSKLFRQIGLTEKQEEDHKKADISETITIEDLEAK
97
P13848
2
98
99%
UniRef90_P13848
2
98
secondary structure
helix
5
16
secondary structure
helix
22
77
pfam
PF11418.5
Scaffolding_pro
2
98
B
Head morphogenesis protein
Bacillus phage phi29
PLKPEEHEDILNKLLDPELAQSERTEALQQLRVNYGSFVSEYNDLTKSHEKLAAEKDDLIVSNSKLFRQIGLTEKQEEDHKKADISETITIEDLEAK
97
P13848
2
98
99%
UniRef90_P13848
2
98
secondary structure
helix
5
16
secondary structure
helix
22
73
pfam
PF11418.5
Scaffolding_pro
2
98
The subunits in the structure are bound via coiled coil interactions (PMID:12778115). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
1noh
4iff
4xa1
MF4130001
Tetrabrachion tetramerization region
1fe6
X-ray
1.80
homotetramer
Staphylothermus marinus
10966648
Stetefeld J, Jenny M, Schulthess T, Landwehr R, Engel J, Kammerer RA
Crystal structure of a naturally occurring parallel right-handed coiled coil tetramer.
Nat. Struct. Biol.
2000
9
7
772-6
The crystal structure of a polypeptide chain fragment from the surface layer protein tetrabrachion from Staphylothermus marinus has been determined at 1.8 A resolution. As proposed on the basis of the presence of 11-residue repeats, the polypeptide chain fragment forms a parallel right-handed coiled coil structure. Complementary hydrophobic interactions and complex networks of surface salt bridges result in an extremely thermostable tetrameric structure with remarkable properties. In marked contrast to left-handed coiled coil tetramers, the right-handed coiled coil reveals large hydrophobic cavities that are filled with water molecules. As a consequence, the packing of the hydrophobic core differs markedly from that of a right-handed parallel coiled coil tetramer that was designed on the basis of left-handed coiled coil structures.
GO:0016021
integral component of membrane
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
1
Coils and zippers
Coiled coil (tetrameric)
A
Tetrabrachion (Precursor)
Staphylothermus marinus
GSIINETADDIVYRLTVIIDDRYESLKNLITLRADRLEMIINDNVSTILASG
52
Q54436
1236
1287
3.4%
UniRef90_Q54436
1237
1286
secondary structure
helix
1238
1286
pfam
PF11401.5
Tetrabrachion
1238
1286
B
Tetrabrachion (Precursor)
Staphylothermus marinus
GSIINETADDIVYRLTVIIDDRYESLKNLITLRADRLEMIINDNVSTILASG
52
Q54436
1236
1287
3.4%
UniRef90_Q54436
1237
1286
secondary structure
helix
1238
1286
pfam
PF11401.5
Tetrabrachion
1238
1286
C
Tetrabrachion (Precursor)
Staphylothermus marinus
GSIINETADDIVYRLTVIIDDRYESLKNLITLRADRLEMIINDNVSTILASG
52
Q54436
1236
1287
3.4%
UniRef90_Q54436
1237
1286
secondary structure
helix
1240
1286
pfam
PF11401.5
Tetrabrachion
1238
1286
D
Tetrabrachion (Precursor)
Staphylothermus marinus
GSIINETADDIVYRLTVIIDDRYESLKNLITLRADRLEMIINDNVSTILASG
52
Q54436
1236
1287
3.4%
UniRef90_Q54436
1237
1286
secondary structure
helix
1238
1284
pfam
PF11401.5
Tetrabrachion
1238
1286
The subunits in the structure are bound via coiled coil interactions (PMID:10966648). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
1ybk
5jr5
MF4140001
Virion-associated protein P3
3f6n
X-ray
3.10
homotetramer
Cauliflower mosaic virus
20181714
Hoh F, Uzest M, Drucker M, Plisson-Chastang C, Bron P, Blanc S, Dumas C
Structural insights into the molecular mechanisms of cauliflower mosaic virus transmission by its insect vector.
J. Virol.
2010
9
84
4706-13
Cauliflower mosaic virus (CaMV) is transmitted from plant to plant through a seemingly simple interaction with insect vectors. This process involves an aphid receptor and two viral proteins, P2 and P3. P2 binds to both the aphid receptor and P3, itself tightly associated with the virus particle, with the ensemble forming a transmissible viral complex. Here, we describe the conformations of both unliganded CaMV P3 protein and its virion-associated form. X-ray crystallography revealed that the N-terminal domain of unliganded P3 is a tetrameric parallel coiled coil with a unique organization showing two successive four-stranded subdomains with opposite supercoiling handedness stabilized by a ring of interchain disulfide bridges. A structural model of virus-liganded P3 proteins, folding as an antiparallel coiled-coil network coating the virus surface, was derived from molecular modeling. Our results highlight the structural and biological versatility of this coiled-coil structure and provide new insights into the molecular mechanisms involved in CaMV acquisition and transmission by the insect vector.
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
1
Coils and zippers
Coiled coil (tetrameric)
A
Virion-associated protein
Cauliflower mosaic virus
MANLNQIQKEVSEILSDQKSMKADIKAILELLGSQNPIKESLETVAAKIVNDLTKLINDCPCNKEILEALGTQPKEQLIEQPKEKGKGLNLGKYSYPNYGVGNEELGSSGNPKALTWPFKAPAGWPNQF
129
P03551
1
129
100%
UniRef90_P03551
1
129
secondary structure
helix
4
34
secondary structure
helix
38
58
secondary structure
helix
63
70
pfam
PF03310.10
Cauli_DNA-bind
4
124
B
Virion-associated protein
Cauliflower mosaic virus
MANLNQIQKEVSEILSDQKSMKADIKAILELLGSQNPIKESLETVAAKIVNDLTKLINDCPCNKEILEALGTQPKEQLIEQPKEKGKGLNLGKYSYPNYGVGNEELGSSGNPKALTWPFKAPAGWPNQF
129
P03551
1
129
100%
UniRef90_P03551
1
129
secondary structure
helix
3
33
secondary structure
helix
38
59
secondary structure
helix
63
70
pfam
PF03310.10
Cauli_DNA-bind
4
124
C
Virion-associated protein
Cauliflower mosaic virus
MANLNQIQKEVSEILSDQKSMKADIKAILELLGSQNPIKESLETVAAKIVNDLTKLINDCPCNKEILEALGTQPKEQLIEQPKEKGKGLNLGKYSYPNYGVGNEELGSSGNPKALTWPFKAPAGWPNQF
129
P03551
1
129
100%
UniRef90_P03551
1
129
secondary structure
helix
3
33
secondary structure
helix
38
57
secondary structure
helix
63
69
pfam
PF03310.10
Cauli_DNA-bind
4
124
D
Virion-associated protein
Cauliflower mosaic virus
MANLNQIQKEVSEILSDQKSMKADIKAILELLGSQNPIKESLETVAAKIVNDLTKLINDCPCNKEILEALGTQPKEQLIEQPKEKGKGLNLGKYSYPNYGVGNEELGSSGNPKALTWPFKAPAGWPNQF
129
P03551
1
129
100%
UniRef90_P03551
1
129
secondary structure
helix
4
33
secondary structure
helix
38
57
secondary structure
helix
63
70
pfam
PF03310.10
Cauli_DNA-bind
4
124
The subunits in the structure are bound via coiled coil interactions (PMID:20181714). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
3k4t
MF5110001
Assembly domain of cartilage oligomeric matrix protein (rat)
1fbm
X-ray
2.70
homopentamer
Rattus norvegicus
9736606
Guo Y, Bozic D, Malashkevich VN, Kammerer RA, Schulthess T, Engel J
All-trans retinol, vitamin D and other hydrophobic compounds bind in the axial pore of the five-stranded coiled-coil domain of cartilage oligomeric matrix protein.
EMBO J.
1998
18
17
5265-72
The potential storage and delivery function of cartilage oligomeric matrix protein (COMP) for cell signaling molecules was explored by binding hydrophobic compounds to the recombinant five-stranded coiled-coil domain of COMP. Complex formation with benzene, cyclohexane, vitamin D3 and elaidic acid was demonstrated through increases in denaturation temperatures of 2-10 degreesC. For all-trans retinol and all-trans retinoic acid, an equilibrium dissociation constant KD = 0.6 microM was evaluated by fluorescence titration. Binding of benzene and all-trans retinol into the hydrophobic axial pore of the COMP coiled-coil domain was proven by the X-ray crystal structures of the corresponding complexes at 0.25 and 0.27 nm resolution, respectively. Benzene binds with its plane perpendicular to the pore axis. The binding site is between the two internal rings formed by Leu37 and Thr40 pointing into the pore of the COMP coiled-coil domain. The retinol beta-ionone ring is positioned in a hydrophobic environment near Thr40, and the 1.1 nm long isoprene tail follows a completely hydrophobic region of the pore. Its terminal hydroxyl group complexes with a ring of the five side chains of Gln54. A mutant in which Gln54 is replaced by Ile binds all-trans retinol with affinity similar to the wild-type, demonstrating that hydrophobic interactions are predominant.
GO:0005509
calcium ion binding
GO:0005499
vitamin D binding
GO:0005201
extracellular matrix structural constituent
GO:0001968
fibronectin binding
GO:0008201
heparin binding
GO:0006915
apoptotic process
GO:0030198
extracellular matrix organization
GO:0007155
cell adhesion
GO:0005578
proteinaceous extracellular matrix
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
5
1
Coils and zippers
Coiled coil (pentameric)
A
Cartilage oligomeric matrix protein
Rattus norvegicus
MDLAPQMLRELQETNAALQDVRELLRQQVKEITFLKNTVMECDACG
46
P35444
27
72
6.1%
UniRef90_P49747
29
73
secondary structure
helix
30
66
pfam
PF11598.5
COMP
28
72
B
Cartilage oligomeric matrix protein
Rattus norvegicus
MDLAPQMLRELQETNAALQDVRELLRQQVKEITFLKNTVMECDACG
46
P35444
27
72
6.1%
UniRef90_P49747
29
73
secondary structure
helix
30
67
pfam
PF11598.5
COMP
28
72
C
Cartilage oligomeric matrix protein
Rattus norvegicus
MDLAPQMLRELQETNAALQDVRELLRQQVKEITFLKNTVMECDACG
46
P35444
27
72
6.1%
UniRef90_P49747
29
73
secondary structure
helix
30
66
secondary structure
helix
69
71
pfam
PF11598.5
COMP
28
72
D
Cartilage oligomeric matrix protein
Rattus norvegicus
MDLAPQMLRELQETNAALQDVRELLRQQVKEITFLKNTVMECDACG
46
P35444
27
72
6.1%
UniRef90_P49747
29
73
secondary structure
helix
30
66
pfam
PF11598.5
COMP
28
72
E
Cartilage oligomeric matrix protein
Rattus norvegicus
MDLAPQMLRELQETNAALQDVRELLRQQVKEITFLKNTVMECDACG
46
P35444
27
72
6.1%
UniRef90_P49747
29
73
secondary structure
helix
30
66
pfam
PF11598.5
COMP
28
72
The subunits in the structure are bound via coiled coil interactions (PMID:9736606). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
1vdf
MF5110002
Assembly domain of cartilage oligomeric matrix protein (mouse)
1mz9
X-ray
1.70
homopentamer
Mus musculus
12426368
Ozbek S, Engel J, Stetefeld J
Storage function of cartilage oligomeric matrix protein: the crystal structure of the coiled-coil domain in complex with vitamin D(3).
EMBO J.
2002
22
21
5960-8
The five-stranded coiled-coil domain of cartilage oligomeric matrix protein (COMPcc) forms a continuous axial pore with binding capacities for hydrophobic compounds, including prominent cell signalling molecules. Here, we report the X-ray structure of the COMPcc domain in complex with vitamin D(3) at 1.7 A resolution. The COMPcc pentamer harbours two molecules of the steroid hormone precursor in a planar s-trans conformation of the conjugated triene, with the aliphatic tails lying along the molecule axis. A hydrophilic ring of five Gln54 side chains divides the channel into two hydrophobic compartments in which the bound vitamin D(3) pair is fixed in a head-to-head orientation. Vitamin D(3) binding induces a volumetric increase of the cavities of approximately 30% while the main chain distances of the pentamer are retained. This adaptation to the bulky ring systems of the ligands is accomplished by a rotamer re-orientation of beta-branched side chains that form the knobs into holes of the coiled-coil structure. Compared with binding of vitamin D and retinoic acid by their classical receptors, COMP exerts a distinct mechanism of interaction mainly defined by the pattern of hydrophobic core residues.
GO:0005518
collagen binding
GO:0008201
heparin binding
GO:0005509
calcium ion binding
GO:0002020
protease binding
GO:0043395
heparan sulfate proteoglycan binding
GO:0007155
cell adhesion
GO:0006915
apoptotic process
GO:0003417
growth plate cartilage development
GO:0043066
negative regulation of apoptotic process
GO:0060173
limb development
GO:0070062
extracellular exosome
GO:0005578
proteinaceous extracellular matrix
GO:0005615
extracellular space
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
5
1
Coils and zippers
Coiled coil (pentameric)
A
Cartilage oligomeric matrix protein
Mus musculus
MDLAPQMLRELQETNAALQDVRELLRQQVKEITFLKNTVMECDAC
45
Q9R0G6
27
71
6%
UniRef90_Q9R0G6
28
71
secondary structure
helix
30
66
pfam
PF11598.5
COMP
28
72
B
Cartilage oligomeric matrix protein
Mus musculus
MDLAPQMLRELQETNAALQDVRELLRQQVKEITFLKNTVMECDAC
45
Q9R0G6
27
71
6%
UniRef90_Q9R0G6
28
71
secondary structure
helix
30
66
pfam
PF11598.5
COMP
28
72
C
Cartilage oligomeric matrix protein
Mus musculus
MDLAPQMLRELQETNAALQDVRELLRQQVKEITFLKNTVMECDAC
45
Q9R0G6
27
71
6%
UniRef90_Q9R0G6
28
71
secondary structure
helix
30
66
pfam
PF11598.5
COMP
28
72
D
Cartilage oligomeric matrix protein
Mus musculus
MDLAPQMLRELQETNAALQDVRELLRQQVKEITFLKNTVMECDAC
45
Q9R0G6
27
71
6%
UniRef90_Q9R0G6
28
71
secondary structure
helix
30
66
pfam
PF11598.5
COMP
28
72
E
Cartilage oligomeric matrix protein
Mus musculus
MDLAPQMLRELQETNAALQDVRELLRQQVKEITFLKNTVMECDAC
45
Q9R0G6
27
71
6%
UniRef90_Q9R0G6
28
71
secondary structure
helix
30
66
pfam
PF11598.5
COMP
28
72
The subunits in the structure are bound via coiled coil interactions (PMID:12426368). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
3v2n
3v2p
3v2q
3v2r
MF2110006
Leucine zipper domain of the c-Jun homodimer
1jun
NMR
homodimer
Serinus canaria
8662824
Junius FK, O'Donoghue SI, Nilges M, Weiss AS, King GF
High resolution NMR solution structure of the leucine zipper domain of the c-Jun homodimer.
J. Biol. Chem.
1996
23
271
13663-7
The solution structure of the c-Jun leucine zipper domain has been determined to high resolution using a new calculation protocol designed to handle highly ambiguous sets of interproton distance restraints. The domain comprises a coiled coil of parallel alpha-helices in which most of the hydrophobic residues are buried at the highly symmetrical dimer interface; this interface extends over 10 helical turns and is the most elongated protein domain solved to date using NMR methods. The backbone fold is very similar to that seen in crystal structures of the GCN4 and Jun-Fos leucine zippers; however, in contrast with these crystal structures, the Jun leucine zipper dimer appears to be devoid of favorable intermolecular electrostatic interactions. A polar asparagine residue, located at the dimer interface, forms the sole point of asymmetry in the structure; furthermore, the side chain of this residue is disordered due to motional averaging. This residue, which is highly conserved in the leucine zipper family of transcription factors, provides a destabilizing influence that is likely to facilitate the rapid exchange of zipper strands in vivo.
GO:0043565
sequence-specific DNA binding
GO:0003700
transcription factor activity, sequence-specific DNA binding
GO:0044212
transcription regulatory region DNA binding
GO:0007265
Ras protein signal transduction
GO:0006355
regulation of transcription, DNA-templated
GO:0006351
transcription, DNA-templated
GO:0005634
nucleus
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Coils and zippers
Leucine zipper (dimeric)
A
Transcription factor AP-1
Serinus canaria
CGGRIARLEEKVKTLKAQNSELASTANMLREQVAQLKQKVMNY
43
P54864
259
298
12.7%
UniRef90_P18870
259
298
secondary structure
helix
259
295
pfam
PF00170.18
bZIP_1
233
296
B
Transcription factor AP-1
Serinus canaria
CGGRIARLEEKVKTLKAQNSELASTANMLREQVAQLKQKVMNY
43
P54864
259
298
12.7%
UniRef90_P18870
259
298
secondary structure
helix
259
295
pfam
PF00170.18
bZIP_1
233
296
The subunits in the structure are bound via coiled coil interactions (PMID:8662824). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure. Leucine zippers, phenylalanine zippers and alanine zippers are subclasses of coiled coils where the hydrophobic interactions between subunits are predominantly formed by leucine, phenylalanine or alanine residues, respectively.
1fos
1jnm
1s9k
1t2k
5t01
MF2110007
Delta sleep-inducing peptide immunoreactive peptide A homolog
1dip
NMR
homodimer
Sus scrofa
9388238
Seidel G, Adermann K, Schindler T, Ejchart A, Jaenicke R, Forssmann WG, Rösch P
Solution structure of porcine delta sleep-inducing peptide immunoreactive peptide A homolog of the shortsighted gene product.
J. Biol. Chem.
1997
49
272
30918-27
The 77-residue delta sleep-inducing peptide immunoreactive peptide (DIP) is a close homolog of the Drosophila melanogaster shortsighted gene product. Porcine DIP (pDIP) and a peptide containing a leucine zipper-related partial sequence of pDIP, pDIP(9-46), was synthesized and studied by circular dichroism and nuclear magnetic resonance spectroscopy in combination with molecular dynamics calculations. Ultracentrifugation, size exclusion chromatography, and model calculations indicated that pDIP forms a dimer. This was confirmed by the observation of concentration-dependent thermal folding-unfolding transitions. From CD spectroscopy and thermal folding-unfolding transitions of pDIP(9-46), it was concluded that the dimerization of pDIP is a result of interaction between helical structures localized in the leucine zipper motif. The three-dimensional structure of the protein was determined with a modified simulated annealing protocol using experimental data derived from nuclear magnetic resonance spectra and a modeling approach based on an established strategy for coiled coil structures. The left-handed super helical structure of the leucine zipper type sequence resulting from the modeling approach is in agreement with known leucine zipper structures. In addition to the hydrophobic interactions between the amino acids at the heptade positions a and d, the structure of pDIP is stabilized by the formation of interhelical i to i' + 5 salt bridges. This result was confirmed by the pH dependence of the thermal-folding transitions. In addition to the amphipatic helix of the leucine zipper, a second helix is formed in the NH2-terminal part of pDIP. This helix exhibits more 310-helix character and is less stable than the leucine zipper helix. For the COOH-terminal region of pDIP no elements of regular secondary structure were observed.
GO:0003700
transcription factor activity, sequence-specific DNA binding
GO:0006355
regulation of transcription, DNA-templated
GO:0070236
negative regulation of activation-induced cell death of T cells
GO:0005634
nucleus
GO:0005737
cytoplasm
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Coils and zippers
Leucine zipper (dimeric)
A
TSC22 domain family protein 3
Sus scrofa
MDLVKNHLMYAVREEVEILKEQIRELVEKNSQLERENTLLKTLASPEQLEKFQSRLSPEEPAPETPEAPEAPGGSAV
77
P80220
1
77
100%
UniRef90_P80220
1
77
secondary structure
helix
7
10
secondary structure
helix
17
43
pfam
PF01166.15
TSC22
1
57
B
TSC22 domain family protein 3
Sus scrofa
MDLVKNHLMYAVREEVEILKEQIRELVEKNSQLERENTLLKTLASPEQLEKFQSRLSPEEPAPETPEAPEAPGGSAV
77
P80220
1
77
100%
UniRef90_P80220
1
77
secondary structure
helix
4
10
secondary structure
helix
16
44
pfam
PF01166.15
TSC22
1
57
The subunits in the structure are bound via coiled coil interactions (PMID:9388238). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure. Leucine zippers, phenylalanine zippers and alanine zippers are subclasses of coiled coils where the hydrophobic interactions between subunits are predominantly formed by leucine, phenylalanine or alanine residues, respectively.
MF2110008
VBP leucine zipper
4u5t
X-ray
3.30
homodimer
Gallus gallus
22851716
Zhao J, Stagno JR, Varticovski L, Nimako E, Rishi V, McKinnon K, Akee R, Shoemaker RH, Ji X, Vinson C
P6981, an arylstibonic acid, is a novel low nanomolar inhibitor of cAMP response element-binding protein binding to DNA.
Mol. Pharmacol.
2012
5
82
814-23
Several basic leucine zipper (B-ZIP) transcription factors have been implicated in cancer, substance abuse, and other pathological conditions. We previously identified arylstibonic acids that bind to B-ZIP proteins and inhibit their interaction with DNA. In this study, we used electrophoretic mobility shift assay to analyze 46 arylstibonic acids for their activity to disrupt the DNA binding of three B-ZIP [CCAAT/enhancer-binding protein α, cyclic AMP-response element-binding protein (CREB), and vitellogenin gene-binding protein (VBP)] and two basic helix-loop-helix leucine zipper (B-HLH-ZIP) [USF (upstream stimulating factor) and Mitf] proteins. Twenty-five arylstibonic acids showed activity at micromolar concentrations. The most active compound, P6981 [2-(3-stibonophenyl)malonic acid], had half-maximal inhibition at ~5 nM for CREB. Circular dichroism thermal denaturation studies indicated that P6981 binds both the B-ZIP domain and the leucine zipper. The crystal structure of an arylstibonic acid, NSC13778, bound to the VBP leucine zipper identified electrostatic interactions between both the stibonic and carboxylic acid groups of NSC13778 [(E)-3-(3-stibonophenyl)acrylic acid] and arginine side chains of VBP, which is also involved in interhelical salt bridges in the leucine zipper. P6981 induced GFP-B-ZIP chimeric proteins to partially localize to the cytoplasm, demonstrating that it is active in cells. P6981 inhibited the growth of a patient-derived clear cell sarcoma cell line whose oncogenic potential is driven by a chimeric protein EWS-ATF1 (Ewing's sarcoma protein-activating transcription factor 1), which contains the DNA binding domain of ATF1, a B-ZIP protein. NSC13778 inhibited the growth of xenografted clear cell sarcoma, and no toxicity was observed. These experiments suggest that antimony containing arylstibonic acids are promising leads for suppression of DNA binding activities of B-ZIP and B-HLH-ZIP transcription factors.
GO:0001077
transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0000977
RNA polymerase II regulatory region sequence-specific DNA binding
GO:0007275
multicellular organism development
GO:0006366
transcription from RNA polymerase II promoter
GO:0045944
positive regulation of transcription from RNA polymerase II promoter
GO:0005634
nucleus
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Coils and zippers
Leucine zipper (dimeric)
A
Transcription factor VBP
Gallus gallus
RDPDLEIRAAFLEKENTALRTEVAELRKEVGRCKNIVSK
39
Q92172
271
305
11%
UniRef90_Q92172
271
305
secondary structure
helix
271
303
pfam
PF07716.12
bZIP_2
242
295
B
Transcription factor VBP
Gallus gallus
RDPDLEIRAAFLEKENTALRTEVAELRKEVGRCKNIVSK
39
Q92172
271
305
11%
UniRef90_Q92172
271
305
secondary structure
helix
271
303
pfam
PF07716.12
bZIP_2
242
295
The subunits in the structure are bound via coiled coil interactions (PMID:22851716). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure. Leucine zippers, phenylalanine zippers and alanine zippers are subclasses of coiled coils where the hydrophobic interactions between subunits are predominantly formed by leucine, phenylalanine or alanine residues, respectively.
A
A close homologue sharing the same Pfam domain (PF07716.12) has been experimentally characterized as disordered in DisProt entry DP00083.
B
A close homologue sharing the same Pfam domain (PF07716.12) has been experimentally characterized as disordered in DisProt entry DP00083.
MF2100004
SH2B adapter protein 2 dimerization domain
1q2h
X-ray
1.70
homodimer
Homo sapiens
15378031
Dhe-Paganon S, Werner ED, Nishi M, Hansen L, Chi YI, Shoelson SE
A phenylalanine zipper mediates APS dimerization.
Nat. Struct. Mol. Biol.
2004
10
11
968-74
The APS, SH2-B and LNK proteins are adapters that activate and modulate receptor tyrosine kinase and JAK/STAT signaling. We now show that a conserved N-terminal domain mediates APS homodimerization. We determined the crystal structure of the dimerization domain at a resolution of 1.7 A using bromide ion MAD phasing. Each molecule contributes two helices to a compact four-helix bundle having a bisecting-U topology. Its most conspicuous feature is a stack of interdigitated phenylalanine side chains at the domain core. These residues create a new motif we refer to as a 'phenylalanine zipper,' which is critical to dimerization. A newly developed bridging yeast tri-hybrid assay showed that APS dimerizes JAK2, insulin receptor and IGF1 receptor kinases using its SH2 and dimerization domains. Dimerization via the phenylalanine zipper domain provides a mechanism for activating and modulating tyrosine kinase activity even in the absence of extracellular ligands.
GO:0004871
signal transducer activity
GO:0005070
SH3/SH2 adaptor activity
GO:0008269
JAK pathway signal transduction adaptor activity
GO:0035556
intracellular signal transduction
GO:0007596
blood coagulation
GO:0008286
insulin receptor signaling pathway
GO:0046425
regulation of JAK-STAT cascade
GO:0009967
positive regulation of signal transduction
GO:0005829
cytosol
GO:0005886
plasma membrane
Chain C was removed as chains A and B represent the biologically relevant dimer.
2
1
Coils and zippers
Phenylalanine zipper (dimeric, forming a 4-helix bundle)
A
SH2B adapter protein 2
Homo sapiens
GSHMPDWRQFCELHAQAAAVDFAHKFCRFLRDNPAYDTPDAGASFSRHFAANFLDVFGEEVRRVLVAGP
69
O14492
17
85
10.9%
UniRef90_O14492
20
85
secondary structure
helix
23
48
secondary structure
helix
50
52
secondary structure
helix
57
82
pfam
PF08916.8
Phe_ZIP
22
78
B
SH2B adapter protein 2
Homo sapiens
GSHMPDWRQFCELHAQAAAVDFAHKFCRFLRDNPAYDTPDAGASFSRHFAANFLDVFGEEVRRVLVAGP
69
O14492
17
85
10.9%
UniRef90_O14492
20
85
secondary structure
helix
23
48
secondary structure
helix
50
52
secondary structure
helix
57
79
pfam
PF08916.8
Phe_ZIP
22
78
The subunits in the structure are bound via coiled coil interactions (PMID:15378031). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure. Leucine zippers, phenylalanine zippers and alanine zippers are subclasses of coiled coils where the hydrophobic interactions between subunits are predominantly formed by leucine, phenylalanine or alanine residues, respectively.
MF2202001
GTPase binding domain of neural Wiskott-Aldrich syndrome protein in complex with E. coli EspF(U)
2lnh
NMR
heterodimer
Homo sapiens / Escherichia coli O157:H7
22921828
Aitio O, Hellman M, Skehan B, Kesti T, Leong JM, Saksela K, Permi P
Enterohaemorrhagic Escherichia Coli Exploits a Tryptophan Switch to Hijack Host F-Actin Assembly.
Structure
2012
Intrinsically disordered protein (IDP)-mediated interactions are often characterized by low affinity but high specificity. These traits are essential in signaling and regulation that require reversibility. Enterohaemorrhagic Escherichia coli (EHEC) exploit this situation by commandeering host cytoskeletal signaling to stimulate actin assembly beneath bound bacteria, generating "pedestals" that promote intestinal colonization. EHEC translocates two proteins, EspF(U) and Tir, which form a complex with the host protein IRTKS. The interaction of this complex with N-WASP triggers localized actin polymerization. We show that EspF(U) is an IDP that contains a transiently α-helical N-terminus and dynamic C-terminus. Our structure shows that single EspF(U) repeat forms a high-affinity trimolecular complex with N-WASP and IRTKS. We demonstrate that bacterial and cellular ligands interact with IRTKS SH3 in a similar fashion, but the bacterial protein has evolved to outcompete cellular targets by utilizing a tryptophan switch that offers superior binding affinity enabling EHEC-induced pedestal formation.
Chain B was removed as it is ordered and does not directly contribute to the interaction between chains A and C. Chain C was truncated to exclude the region in contact with chain B.
2
2
Other
Other
A
Neural Wiskott-Aldrich syndrome protein
Homo sapiens
GSNFQHIGHVGWDPNTGFDLNNLDPELKNLFDMCGISEAQLKDRETSKVIYDFIEKTGGVEAVKN
65
O00401
206
270
12.9%
UniRef90_O00401
207
270
secondary structure
beta
217
218
secondary structure
beta
222
223
secondary structure
helix
225
227
secondary structure
helix
232
239
secondary structure
helix
243
246
secondary structure
helix
252
262
secondary structure
helix
265
269
pfam
PF00786.25
PBD
202
261
C
Secreted effector protein EspF(U)
Escherichia coli O157:H7
GLPDVAQRLMQHLAEHGIQPARNMAEHIPPAPNWPAPTPPVQNEQSRP
48
P0DJ89
220
267
14.2%
UniRef90_P0DJ88
221
267
secondary structure
helix
222
232
pfam
PF04806.9
EspF
190
236
pfam
PF04806.9
EspF
237
283
A
A close homologue sharing the same Pfam domain (PF00786.25) has been experimentally characterized as disordered in DisProt entry DP00215 and IDEAL entry IID00269.
C
The 221-314 region described in IDEAL entry IID90008 covers 97.9% of the sequence present in the structure. The interacting region has also been shown to be disordered in the structure's source publication (PMID:22921828).
MF2220001
CesA-EspA complex
1xou
X-ray
2.80
heterodimer
Escherichia coli
15619638
Yip CK, Finlay BB, Strynadka NC
Structural characterization of a type III secretion system filament protein in complex with its chaperone.
Nat. Struct. Mol. Biol.
2005
1
12
75-81
The type III secretion system (TTSS) mediates the specific translocation of bacterial proteins into the cytoplasm of eukaryotic cells, a process essential for the virulence of many Gram-negative pathogens. The enteropathogenic Escherichia coli TTSS protein EspA forms a hollow extracellular filament believed to be a molecular conduit for type III protein translocation. Structural analysis of EspA has been hampered by its polymeric nature. We show that EspA alone is sufficient to form filamentous structures in the absence of other pathogenicity island-encoded proteins. CesA is the recently proposed chaperone of EspA, and we demonstrate that CesA traps EspA in a monomeric state and inhibits its polymerization. Crystallographic analysis of the heterodimeric CesA-EspA complex at a resolution of 2.8 A reveals that EspA contains two long a-helices, which are involved in extensive coiled-coil interactions with CesA.
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
2
Coils and zippers
Coiled coil (dimeric, forming a 4-helix bundle)
A
EspA
Escherichia coli
MDTSTTASVASANASTSTSMAYDLGSMSKDDVIDLFNKLGVFQAAILMFAYMYQAQSDLSIAKFADMNEASKESTTAQKMANLVDAKIADVQSSSDKNAKAQLPDEVISYINDPRNDITISGIDNINAQLGAGDLQTVKAAISAKANNLTTTVNNSQLEIQQMSNTLNLLTSARSDMQSLQYRTISGISLGK
192
Q47184
1
192
100%
UniRef90_Q47184
1
192
secondary structure
helix
151
162
secondary structure
helix
164
176
secondary structure
helix
178
190
pfam
PF03433.10
EspA
2
185
B
L0052
Escherichia coli
MGIVSQTRNKELLDKKIRSEIEAIKKIIAEFDVVKESVNELSEKAKTDPQAAEKLNKLIEGYTYGEERKLYDSALSKIEKLIETLSPARSKSQST
95
O52124
1
95
88.8%
UniRef90_O52124
1
95
secondary structure
helix
3
47
secondary structure
helix
49
64
secondary structure
helix
66
83
pfam
PF11439.5
T3SchapCesA
1
95
The subunits in the structure are bound via coiled coil interactions (PMID:15619638). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
MF2120012
Cell division factor ZapA (mutant)
2mmv
NMR
homodimer
Geobacillus kaustophilus
Nogueira, M.L., Sforca, M., Zeri, A.
Zapa mutant dimer from B. stearothermophilus
To be published
-
GO:0090529
cell septum assembly
GO:0005737
cytoplasm
GO:0005886
plasma membrane
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Coils and zippers
Coiled coil (dimeric)
A
Cell division protein ZapA
Geobacillus kaustophilus
GSHMTEQPKTRVSVRIYGQDYTIVGAESPAHIRLVAAFVDDKMHEFSEKQPMLDVPKLAVLTAVQIASEYLKLKEEYQRLREQLKK
86
Q5KWF5
1
83
91.2%
UniRef90_Q5KWF5
1
83
secondary structure
beta
8
13
secondary structure
beta
16
21
secondary structure
helix
28
44
secondary structure
helix
53
81
pfam
PF05164.10
ZapA
9
89
B
Cell division protein ZapA
Geobacillus kaustophilus
GSHMTEQPKTRVSVRIYGQDYTIVGAESPAHIRLVAAFVDDKMHEFSEKQPMLDVPKLAVLTAVQIASEYLKLKEEYQRLREQLKK
86
Q5KWF5
1
83
91.2%
UniRef90_Q5KWF5
1
83
secondary structure
beta
8
13
secondary structure
beta
16
21
secondary structure
helix
28
44
secondary structure
helix
52
80
pfam
PF05164.10
ZapA
9
89
The subunits in the structure are bound via coiled coil interactions. Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
MF2120013
5-hydroxyisourate hydrolase (Brucella melitensis)
4q14
X-ray
1.70
homodimer
Brucella melitensis biotype 1
Seattle Structural Genomics Center for Infectious Disease (SSGCID), Abendroth, J., Lorimer, D., Edwards, T.E.
Crystal structure of 5-hydroxyisourate hydrolase from Brucella melitensis
To be published
-
GO:0033971
hydroxyisourate hydrolase activity
GO:0006144
purine nucleobase metabolic process
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Transthyretin-like folds
HIUase
A
5-hydroxyisourate hydrolase
Brucella melitensis biotype 1
MAHHHHHHMGTLEAQTQGPGSMGKLSTHVLDTAHGTPAAAMRVELYRIAASGTPELLKRVVTNLDGRTDAPLLSGDEMRTGIYELQFHVAEYFEGRGAELAHEPFLDLIPIRFGIADEDGNYHVPLLVSPWSYSTYRGS
139
Q8YFU1
1
118
100%
UniRef90_Q8YFU1
1
118
secondary structure
beta
3
10
secondary structure
beta
15
16
secondary structure
beta
21
27
secondary structure
beta
33
40
secondary structure
beta
52
52
secondary structure
helix
54
56
secondary structure
beta
60
67
secondary structure
helix
68
74
secondary structure
beta
87
94
secondary structure
beta
100
108
secondary structure
beta
111
115
pfam
PF00576.18
Transthyretin
4
117
B
5-hydroxyisourate hydrolase
Brucella melitensis biotype 1
MAHHHHHHMGTLEAQTQGPGSMGKLSTHVLDTAHGTPAAAMRVELYRIAASGTPELLKRVVTNLDGRTDAPLLSGDEMRTGIYELQFHVAEYFEGRGAELAHEPFLDLIPIRFGIADEDGNYHVPLLVSPWSYSTYRGS
139
Q8YFU1
1
118
100%
UniRef90_Q8YFU1
1
118
secondary structure
beta
3
10
secondary structure
beta
15
16
secondary structure
beta
21
27
secondary structure
beta
33
40
secondary structure
beta
52
53
secondary structure
helix
54
56
secondary structure
beta
60
67
secondary structure
helix
68
74
secondary structure
beta
87
94
secondary structure
beta
100
108
secondary structure
beta
111
115
pfam
PF00576.18
Transthyretin
4
117
The protein belongs to the 5-hydroxyisourate hydrolase (HIUase)/transthyretin protein family. Accordingly, the complex adopts a transthyterin-like fold (based on Pfam entry PF00576.18). Transthyretin was shown in calorimetrics experiments to follow two-state folding/binding kinetics with the emergence of structure being linked to oligomerization (PMID:11152276).
MF4120002
5-hydroxyisourate hydrolase (Salmonella dublin)
2gpz
X-ray
2.50
homotetramer (dimer of dimers)
Salmonella typhi
16787778
Hennebry SC, Law RH, Richardson SJ, Buckle AM, Whisstock JC
The crystal structure of the transthyretin-like protein from Salmonella dublin, a prokaryote 5-hydroxyisourate hydrolase.
J. Mol. Biol.
2006
5
359
1389-99
The mechanism of binding of thyroid hormones by the transport protein transthyretin (TTR) in vertebrates is structurally well characterised. However, a homologous family of transthyretin-like proteins (TLPs) present in bacteria as well as eukaryotes do not bind thyroid hormones, instead they are postulated to perform a role in the purine degradation pathway and function as 5-hydroxyisourate hydrolases. Here we describe the 2.5 Angstroms X-ray crystal structure of the TLP from the Gram-negative bacterium Salmonella dublin, and compare and contrast its structure with vertebrate TTRs. The overall architecture of the homotetramer is conserved and, despite low sequence homology with vertebrate TTRs, structural differences within the monomer are restricted to flexible loop regions. However, sequence variation at the dimer-dimer interface has profound consequences for the ligand binding site and provides a structural rationalisation for the absence of thyroid hormone binding affinity in bacterial TLPs: the deep, negatively charged thyroxine-binding pocket that characterises vertebrate TTR contrasts with a shallow and elongated, positively charged cleft in S. dublin TLP. We have demonstrated that Sdu_TLP is a 5-hydroxyisourate hydrolase. Furthermore, using site-directed mutagenesis, we have identified three conserved residues located in this cleft that are critical to the enzyme activity. Together our data reveal that the active site of Sdu_TLP corresponds to the thyroxine binding site in TTRs.
GO:0033971
hydroxyisourate hydrolase activity
GO:0006144
purine nucleobase metabolic process
GO:0042597
periplasmic space
Chains C and D were generated from chains A and B respectively, using the biomatrices described in the original PDB file.
4
1
Transthyretin-like folds
HIUase
A
5-hydroxyisourate hydrolase
Salmonella typhi
MILSVHILDQQTGKPAPGVEVVLEQKKDNGWTQLNTGHTDQDGRIKALWPEKAAAPGDYRVIFKTGQYFESKKLDTFFPEIPVEFHISKTNEHYHVPLLLSQYGYSTYRGS
111
Q8Z7Q6
27
136
80.9%
UniRef90_Q4VYA5
27
136
secondary structure
beta
27
34
secondary structure
beta
39
40
secondary structure
beta
45
51
secondary structure
beta
56
63
secondary structure
beta
69
70
secondary structure
beta
82
88
secondary structure
helix
90
96
secondary structure
beta
106
112
secondary structure
beta
118
120
secondary structure
beta
123
126
secondary structure
beta
129
133
pfam
PF00576.18
Transthyretin
28
135
B
5-hydroxyisourate hydrolase
Salmonella typhi
MILSVHILDQQTGKPAPGVEVVLEQKKDNGWTQLNTGHTDQDGRIKALWPEKAAAPGDYRVIFKTGQYFESKKLDTFFPEIPVEFHISKTNEHYHVPLLLSQYGYSTYRGS
111
Q8Z7Q6
27
136
80.9%
UniRef90_Q4VYA5
27
136
secondary structure
beta
27
34
secondary structure
beta
39
40
secondary structure
beta
45
51
secondary structure
beta
56
63
secondary structure
beta
69
70
secondary structure
beta
82
88
secondary structure
helix
90
96
secondary structure
beta
106
112
secondary structure
beta
118
120
secondary structure
beta
123
126
secondary structure
beta
129
133
pfam
PF00576.18
Transthyretin
28
135
C
5-hydroxyisourate hydrolase
Salmonella typhi
MILSVHILDQQTGKPAPGVEVVLEQKKDNGWTQLNTGHTDQDGRIKALWPEKAAAPGDYRVIFKTGQYFESKKLDTFFPEIPVEFHISKTNEHYHVPLLLSQYGYSTYRGS
111
Q8Z7Q6
27
136
80.9%
UniRef90_Q4VYA5
27
136
secondary structure
beta
27
34
secondary structure
beta
39
40
secondary structure
beta
45
51
secondary structure
beta
56
63
secondary structure
beta
69
70
secondary structure
beta
82
88
secondary structure
helix
90
96
secondary structure
beta
106
112
secondary structure
beta
118
120
secondary structure
beta
123
126
secondary structure
beta
129
133
pfam
PF00576.18
Transthyretin
28
135
D
5-hydroxyisourate hydrolase
Salmonella typhi
MILSVHILDQQTGKPAPGVEVVLEQKKDNGWTQLNTGHTDQDGRIKALWPEKAAAPGDYRVIFKTGQYFESKKLDTFFPEIPVEFHISKTNEHYHVPLLLSQYGYSTYRGS
111
Q8Z7Q6
27
136
80.9%
UniRef90_Q4VYA5
27
136
secondary structure
beta
27
34
secondary structure
beta
39
40
secondary structure
beta
45
51
secondary structure
beta
56
63
secondary structure
beta
69
70
secondary structure
beta
82
88
secondary structure
helix
90
96
secondary structure
beta
106
112
secondary structure
beta
118
120
secondary structure
beta
123
126
secondary structure
beta
129
133
pfam
PF00576.18
Transthyretin
28
135
The protein belongs to the 5-hydroxyisourate hydrolase (HIUase)/transthyretin protein family. Accordingly, the complex adopts a transthyterin-like fold (based on Pfam entry PF00576.18 and the publication PMID:16787778). Transthyretin was shown in calorimetrics experiments to follow two-state folding/binding kinetics with the emergence of structure being linked to oligomerization (PMID:11152276).
MF4120003
5-hydroxyisourate hydrolase (Bacillus subtilis)
2h0e
X-ray
2.20
homotetramer (dimer of dimers)
Bacillus subtilis
16782815
Jung DK, Lee Y, Park SG, Park BC, Kim GH, Rhee S
Structural and functional analysis of PucM, a hydrolase in the ureide pathway and a member of the transthyretin-related protein family.
Proc. Natl. Acad. Sci. U.S.A.
2006
26
103
9790-5
The ureide pathway, which produces ureides from uric acid, is an essential purine catabolic process for storing and transporting the nitrogen fixed in leguminous plants and some bacteria. PucM from Bacillus subtilis was recently characterized and found to catalyze the second reaction of the pathway, hydrolyzing 5-hydroxyisourate (HIU), a product of uricase in the first step. PucM has 121 amino acid residues and shows high sequence similarity to the functionally unrelated protein transthyretin (TTR), a thyroid hormone-binding protein. Therefore, PucM belongs to the TTR-related proteins (TRP) family. The crystal structures of PucM at 2.0 A and its complexes with the substrate analogs 8-azaxanthine and 5,6-diaminouracil reveal that even with their overall structure similarity, homotetrameric PucM and TTR are completely different, both in their electrostatic potential and in the size of the active sites located at the dimeric interface. Nevertheless, the absolutely conserved residues across the TRP family, including His-14, Arg-49, His-105, and the C-terminal Tyr-118-Arg-119-Gly-120-Ser-121, indeed form the active site of PucM. Based on the results of site-directed mutagenesis of these residues, we propose a possible mechanism for HIU hydrolysis. The PucM structure determined for the TRP family leads to the conclusion that diverse members of the TRP family would function similarly to PucM as HIU hydrolase.
GO:0033971
hydroxyisourate hydrolase activity
GO:0006144
purine nucleobase metabolic process
GO:0019628
urate catabolic process
Chains C, D and E were generated from chain A using the biomatrices described in the original PDB file. Chain B was removed as chains A, C, D and E represent the biologically relevant tetramer.
4
1
Transthyretin-like folds
HIUase
A
5-hydroxyisourate hydrolase
Bacillus subtilis
MSEPESLMGKLTTHILDLTCGKPAANVKIGLKRLGESIMKEVYTNNDGRVDVPLLAGEELMSGEYVMEFHAGDYFASKNMNAADQPFLTIVTVRFQLADPDAHYHIPLLLSPFGYQVYRGS
121
O32142
1
114
100%
UniRef90_O32142
1
114
secondary structure
beta
4
6
secondary structure
beta
9
11
secondary structure
beta
16
17
secondary structure
beta
22
27
secondary structure
beta
35
38
secondary structure
beta
50
51
secondary structure
helix
52
53
secondary structure
helix
55
55
secondary structure
beta
61
66
secondary structure
helix
68
72
secondary structure
helix
75
75
secondary structure
beta
88
94
secondary structure
beta
100
102
secondary structure
beta
105
108
secondary structure
beta
111
114
pfam
PF00576.18
Transthyretin
4
113
C
5-hydroxyisourate hydrolase
Bacillus subtilis
MSEPESLMGKLTTHILDLTCGKPAANVKIGLKRLGESIMKEVYTNNDGRVDVPLLAGEELMSGEYVMEFHAGDYFASKNMNAADQPFLTIVTVRFQLADPDAHYHIPLLLSPFGYQVYRGS
121
O32142
1
114
100%
UniRef90_O32142
1
114
secondary structure
beta
4
6
secondary structure
beta
9
11
secondary structure
beta
16
17
secondary structure
beta
22
27
secondary structure
beta
35
38
secondary structure
beta
50
51
secondary structure
helix
52
53
secondary structure
helix
55
55
secondary structure
beta
61
66
secondary structure
helix
68
72
secondary structure
helix
75
75
secondary structure
beta
88
94
secondary structure
beta
100
102
secondary structure
beta
105
108
secondary structure
beta
111
114
pfam
PF00576.18
Transthyretin
4
113
D
5-hydroxyisourate hydrolase
Bacillus subtilis
MSEPESLMGKLTTHILDLTCGKPAANVKIGLKRLGESIMKEVYTNNDGRVDVPLLAGEELMSGEYVMEFHAGDYFASKNMNAADQPFLTIVTVRFQLADPDAHYHIPLLLSPFGYQVYRGS
121
O32142
1
114
100%
UniRef90_O32142
1
114
secondary structure
beta
4
6
secondary structure
beta
9
11
secondary structure
beta
16
17
secondary structure
beta
22
27
secondary structure
beta
35
38
secondary structure
beta
50
51
secondary structure
helix
52
53
secondary structure
helix
55
55
secondary structure
beta
61
66
secondary structure
helix
68
72
secondary structure
helix
75
75
secondary structure
beta
88
94
secondary structure
beta
100
102
secondary structure
beta
105
108
secondary structure
beta
111
114
pfam
PF00576.18
Transthyretin
4
113
E
5-hydroxyisourate hydrolase
Bacillus subtilis
MSEPESLMGKLTTHILDLTCGKPAANVKIGLKRLGESIMKEVYTNNDGRVDVPLLAGEELMSGEYVMEFHAGDYFASKNMNAADQPFLTIVTVRFQLADPDAHYHIPLLLSPFGYQVYRGS
121
O32142
1
114
100%
UniRef90_O32142
1
114
secondary structure
beta
4
6
secondary structure
beta
9
11
secondary structure
beta
16
17
secondary structure
beta
22
27
secondary structure
beta
35
38
secondary structure
beta
50
51
secondary structure
helix
52
53
secondary structure
helix
55
55
secondary structure
beta
61
66
secondary structure
helix
68
72
secondary structure
helix
75
75
secondary structure
beta
88
94
secondary structure
beta
100
102
secondary structure
beta
105
108
secondary structure
beta
111
114
pfam
PF00576.18
Transthyretin
4
113
The protein belongs to the 5-hydroxyisourate hydrolase (HIUase)/transthyretin protein family. Accordingly, the complex adopts a transthyterin-like fold (based on Pfam entry PF00576.18 and the publication PMID:16782815). Transthyretin was shown in calorimetrics experiments to follow two-state folding/binding kinetics with the emergence of structure being linked to oligomerization (PMID:11152276).
2h0f
2h0j
MF4120004
5-hydroxyisourate hydrolase (Klebsiella pneumoniae)
3qva
X-ray
1.75
homotetramer (dimer of dimers)
Klebsiella pneumoniae subsp. pneumoniae
21795808
French JB, Ealick SE
Structural and kinetic insights into the mechanism of 5-hydroxyisourate hydrolase from Klebsiella pneumoniae.
Acta Crystallogr. D Biol. Crystallogr.
2011
Pt 8
67
671-7
The stereospecific oxidative degradation of uric acid to (S)-allantoin has recently been demonstrated to proceed via two unstable intermediates and requires three separate enzymatic reactions. The second step of this reaction, the conversion of 5-hydroxyisourate (HIU) to 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline, is catalyzed by HIU hydrolase (HIUH). The high-resolution crystal structure of HIUH from the opportunistic pathogen Klebsiella pneumoniae (KpHIUH) has been determined. KpHIUH is a homotetrameric protein that, based on sequence and structural similarity, belongs to the transthyretin-related protein family. In addition, the steady-state kinetic parameters for this enzyme and four active-site mutants have been measured. These data provide valuable insight into the functional roles of the active-site residues. Based upon the structural and kinetic data, a mechanism is proposed for the KpHIUH-catalyzed reaction.
GO:0033971
hydroxyisourate hydrolase activity
GO:0006144
purine nucleobase metabolic process
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
1
Transthyretin-like folds
HIUase
A
Transthyretin-like protein
Klebsiella pneumoniae subsp. pneumoniae
ENLYFQGHMSTLSTHILDISTGTPAEGVTVSLSREGETLANLVTNAQGRIATFSAAPLPAGRYCLTAETGAWFARAGRESVFTRAQIDFVIGEAAEDHFHLPFLIAPGGWSTYRGS
116
A6T926
1
108
100%
UniRef90_R4YDW2
1
108
secondary structure
beta
2
2
secondary structure
beta
4
10
secondary structure
beta
15
16
secondary structure
beta
21
26
secondary structure
beta
29
35
secondary structure
beta
41
42
secondary structure
beta
50
50
secondary structure
beta
54
59
secondary structure
helix
61
67
secondary structure
beta
74
82
secondary structure
beta
91
92
secondary structure
beta
95
98
secondary structure
beta
101
105
pfam
PF00576.18
Transthyretin
4
107
B
Transthyretin-like protein
Klebsiella pneumoniae subsp. pneumoniae
ENLYFQGHMSTLSTHILDISTGTPAEGVTVSLSREGETLANLVTNAQGRIATFSAAPLPAGRYCLTAETGAWFARAGRESVFTRAQIDFVIGEAAEDHFHLPFLIAPGGWSTYRGS
116
A6T926
1
108
100%
UniRef90_R4YDW2
1
108
secondary structure
beta
2
10
secondary structure
beta
15
16
secondary structure
beta
21
26
secondary structure
beta
29
35
secondary structure
beta
41
42
secondary structure
beta
50
50
secondary structure
beta
53
59
secondary structure
helix
61
67
secondary structure
beta
74
83
secondary structure
beta
90
92
secondary structure
beta
95
98
secondary structure
beta
101
105
pfam
PF00576.18
Transthyretin
4
107
C
Transthyretin-like protein
Klebsiella pneumoniae subsp. pneumoniae
ENLYFQGHMSTLSTHILDISTGTPAEGVTVSLSREGETLANLVTNAQGRIATFSAAPLPAGRYCLTAETGAWFARAGRESVFTRAQIDFVIGEAAEDHFHLPFLIAPGGWSTYRGS
116
A6T926
1
108
100%
UniRef90_R4YDW2
1
108
secondary structure
beta
2
10
secondary structure
beta
15
16
secondary structure
beta
21
26
secondary structure
beta
29
35
secondary structure
beta
41
42
secondary structure
beta
50
50
secondary structure
beta
53
59
secondary structure
helix
61
67
secondary structure
beta
74
83
secondary structure
beta
90
92
secondary structure
beta
95
98
secondary structure
beta
101
105
pfam
PF00576.18
Transthyretin
4
107
D
Transthyretin-like protein
Klebsiella pneumoniae subsp. pneumoniae
ENLYFQGHMSTLSTHILDISTGTPAEGVTVSLSREGETLANLVTNAQGRIATFSAAPLPAGRYCLTAETGAWFARAGRESVFTRAQIDFVIGEAAEDHFHLPFLIAPGGWSTYRGS
116
A6T926
1
108
100%
UniRef90_R4YDW2
1
108
secondary structure
beta
3
10
secondary structure
beta
15
16
secondary structure
beta
21
26
secondary structure
beta
29
35
secondary structure
beta
41
42
secondary structure
beta
53
59
secondary structure
helix
61
67
secondary structure
beta
74
83
secondary structure
beta
90
92
secondary structure
beta
95
98
secondary structure
beta
101
105
pfam
PF00576.18
Transthyretin
4
107
The protein belongs to the 5-hydroxyisourate hydrolase (HIUase)/transthyretin protein family. Accordingly, the complex adopts a transthyterin-like fold (based on Pfam entry PF00576.18 and the publication PMID:21795808). Transthyretin was shown in calorimetrics experiments to follow two-state folding/binding kinetics with the emergence of structure being linked to oligomerization (PMID:11152276).
MF4120005
5-hydroxyisourate hydrolase (Escherichia coli)
2g2n
X-ray
1.65
homotetramer (dimer of dimers)
Escherichia coli
16723258
Lundberg E, Bäckström S, Sauer UH, Sauer-Eriksson AE
The transthyretin-related protein: structural investigation of a novel protein family.
J. Struct. Biol.
2006
3
155
445-57
The transthyretin-related protein (TRP) family comprises proteins predicted to be structurally related to the homotetrameric transport protein transthyretin (TTR). The function of TRPs is not yet fully established, but recent data suggest that they are involved in purine catabolism. We have determined the three-dimensional structure of the Escherichia coli TRP in two crystal forms; one at 1.65 A resolution in the presence of zinc, and the other at 2.1 A resolution in the presence of zinc and bromide. The structures revealed five zinc-ion-binding sites per monomer. Of these, the zinc ions bound at sites I and II are coordinated in tetrahedral geometries to the side chains of residues His9, His96, His98, Ser114, and three water molecules at the putative ligand-binding site. Of these four residues, His9, His98, and Ser114 are conserved. His9 and His98 bind the central zinc (site I) together with two water molecules. The side chain of His98 also binds to the zinc ion at site II. Bromide ions bind at site I only, replacing one of the water molecules coordinated to the zinc ion. The C-terminal four amino acid sequence motif Y-[RK]-G-[ST] constitutes the signature sequence of the TRP family. Two Tyr111 residues form direct hydrogen bonds to each other over the tetramer interface at the area, which in TTR constitutes the rear part of its thyroxine-binding channel. The putative substrate/ligand-binding channel of TRP is consequently shallower and broader than its counterpart in TTR.
GO:0033971
hydroxyisourate hydrolase activity
GO:0006144
purine nucleobase metabolic process
GO:0042597
periplasmic space
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
1
Transthyretin-like folds
HIUase
A
5-hydroxyisourate hydrolase
Escherichia coli
AQQNILSVHILNQQTGKPAADVTVTLEKKADNGWLQLNTAKTDKDGRIKALWPEQTATTGDYRVVFKTGDYFKKQNLESFFPEIPVEFHINKVNEHYHVPLLLSQYGYSTYRGS
114
P76341
24
137
83.2%
UniRef90_P76341
24
137
secondary structure
beta
29
35
secondary structure
beta
40
41
secondary structure
beta
46
52
secondary structure
beta
57
64
secondary structure
beta
70
71
secondary structure
beta
83
89
secondary structure
helix
91
97
secondary structure
beta
107
113
secondary structure
beta
120
127
secondary structure
beta
130
134
pfam
PF00576.18
Transthyretin
29
136
B
5-hydroxyisourate hydrolase
Escherichia coli
AQQNILSVHILNQQTGKPAADVTVTLEKKADNGWLQLNTAKTDKDGRIKALWPEQTATTGDYRVVFKTGDYFKKQNLESFFPEIPVEFHINKVNEHYHVPLLLSQYGYSTYRGS
114
P76341
24
137
83.2%
UniRef90_P76341
24
137
secondary structure
beta
29
35
secondary structure
beta
40
41
secondary structure
beta
46
53
secondary structure
beta
56
64
secondary structure
beta
70
71
secondary structure
beta
83
89
secondary structure
helix
91
97
secondary structure
beta
107
113
secondary structure
beta
120
127
secondary structure
beta
130
134
pfam
PF00576.18
Transthyretin
29
136
C
5-hydroxyisourate hydrolase
Escherichia coli
AQQNILSVHILNQQTGKPAADVTVTLEKKADNGWLQLNTAKTDKDGRIKALWPEQTATTGDYRVVFKTGDYFKKQNLESFFPEIPVEFHINKVNEHYHVPLLLSQYGYSTYRGS
114
P76341
24
137
83.2%
UniRef90_P76341
24
137
secondary structure
beta
29
35
secondary structure
beta
40
41
secondary structure
beta
46
53
secondary structure
beta
56
64
secondary structure
beta
70
71
secondary structure
beta
83
89
secondary structure
helix
91
97
secondary structure
beta
107
113
secondary structure
beta
120
127
secondary structure
beta
130
134
secondary structure
beta
136
136
pfam
PF00576.18
Transthyretin
29
136
D
5-hydroxyisourate hydrolase
Escherichia coli
AQQNILSVHILNQQTGKPAADVTVTLEKKADNGWLQLNTAKTDKDGRIKALWPEQTATTGDYRVVFKTGDYFKKQNLESFFPEIPVEFHINKVNEHYHVPLLLSQYGYSTYRGS
114
P76341
24
137
83.2%
UniRef90_P76341
24
137
secondary structure
beta
29
35
secondary structure
beta
40
41
secondary structure
beta
46
53
secondary structure
beta
56
64
secondary structure
beta
70
71
secondary structure
beta
83
89
secondary structure
helix
91
97
secondary structure
beta
107
113
secondary structure
beta
120
127
secondary structure
beta
130
134
pfam
PF00576.18
Transthyretin
29
136
The protein belongs to the 5-hydroxyisourate hydrolase (HIUase)/transthyretin protein family. Accordingly, the complex adopts a transthyterin-like fold (based on Pfam entry PF00576.18 and the publication PMID:16723258). Transthyretin was shown in calorimetrics experiments to follow two-state folding/binding kinetics with the emergence of structure being linked to oligomerization (PMID:11152276).
2g2p
2igl
MF4110003
5-hydroxyisourate hydrolase (Danio rerio)
2h1x
X-ray
1.98
homotetramer (dimer of dimers)
Danio rerio
16952372
Zanotti G, Cendron L, Ramazzina I, Folli C, Percudani R, Berni R
Structure of zebra fish HIUase: insights into evolution of an enzyme to a hormone transporter.
J. Mol. Biol.
2006
1
363
1-9
During early vertebrate evolution, a duplication event in the gene encoding 5-hydroxyisourate hydrolase (HIUase), a widely distributed enzyme of purine metabolism, gave rise to transthyretin (TTR), a thyroid hormone transporter. We report here on the crystal structure of zebra fish HIUase in two different crystal forms. Despite the phylogenetic distance, this structure compares well with those of newly characterized bacterial HIUases, especially with regard to catalytic regions, which are highly preserved. Comparison with TTR structure reveals a highly conserved scaffold, harbouring distinct functional sites located in the same regions of the two vertebrate proteins. Residues that are differentially conserved in HIUases compared to TTR map in putative catalytic regions occupying significant portions of the two halves of a central channel that transverses the whole TTR protein. The evolution of TTR has been accompanied by remarkable changes of the HIUase active sites that gave rise to a channel open at both ends, thus allowing free access to hormone molecules.
GO:0033971
hydroxyisourate hydrolase activity
GO:0016811
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides
GO:0019628
urate catabolic process
GO:0006144
purine nucleobase metabolic process
GO:0005777
peroxisome
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
1
Transthyretin-like folds
HIUase
A
5-hydroxyisourate hydrolase
Danio rerio
MAATLLSPLSTHVLNIAQGVPGANMTIVLHRLDPVSSAWNILTTGITNDDGRCPGLITKENFIAGVYKMRFETGKYWDALGETCFYPYVEIVFTITNTSQHYHVPLLLSRFSYSTYRGS
119
Q06S87
20
138
86.2%
UniRef90_Q06S87
20
138
secondary structure
beta
28
29
secondary structure
beta
31
34
secondary structure
beta
39
40
secondary structure
beta
45
51
secondary structure
beta
58
65
secondary structure
beta
71
71
secondary structure
beta
84
90
secondary structure
helix
92
97
secondary structure
beta
108
114
secondary structure
beta
121
122
secondary structure
beta
125
127
secondary structure
beta
131
135
secondary structure
beta
137
137
pfam
PF00576.18
Transthyretin
28
137
B
5-hydroxyisourate hydrolase
Danio rerio
MAATLLSPLSTHVLNIAQGVPGANMTIVLHRLDPVSSAWNILTTGITNDDGRCPGLITKENFIAGVYKMRFETGKYWDALGETCFYPYVEIVFTITNTSQHYHVPLLLSRFSYSTYRGS
119
Q06S87
20
138
86.2%
UniRef90_Q06S87
20
138
secondary structure
beta
28
29
secondary structure
beta
32
34
secondary structure
beta
39
40
secondary structure
beta
45
51
secondary structure
beta
58
65
secondary structure
helix
78
80
secondary structure
beta
84
90
secondary structure
helix
92
97
secondary structure
beta
108
114
secondary structure
beta
121
122
secondary structure
beta
125
128
secondary structure
beta
131
135
secondary structure
beta
137
137
pfam
PF00576.18
Transthyretin
28
137
C
5-hydroxyisourate hydrolase
Danio rerio
MAATLLSPLSTHVLNIAQGVPGANMTIVLHRLDPVSSAWNILTTGITNDDGRCPGLITKENFIAGVYKMRFETGKYWDALGETCFYPYVEIVFTITNTSQHYHVPLLLSRFSYSTYRGS
119
Q06S87
20
138
86.2%
UniRef90_Q06S87
20
138
secondary structure
beta
28
29
secondary structure
beta
31
34
secondary structure
beta
39
40
secondary structure
beta
45
51
secondary structure
beta
58
65
secondary structure
beta
71
71
secondary structure
helix
78
80
secondary structure
beta
84
90
secondary structure
helix
92
98
secondary structure
beta
108
114
secondary structure
beta
121
122
secondary structure
beta
125
127
secondary structure
beta
131
135
secondary structure
beta
137
137
pfam
PF00576.18
Transthyretin
28
137
D
5-hydroxyisourate hydrolase
Danio rerio
MAATLLSPLSTHVLNIAQGVPGANMTIVLHRLDPVSSAWNILTTGITNDDGRCPGLITKENFIAGVYKMRFETGKYWDALGETCFYPYVEIVFTITNTSQHYHVPLLLSRFSYSTYRGS
119
Q06S87
20
138
86.2%
UniRef90_Q06S87
20
138
secondary structure
beta
28
29
secondary structure
beta
31
34
secondary structure
beta
39
40
secondary structure
beta
45
51
secondary structure
beta
58
65
secondary structure
beta
71
71
secondary structure
beta
84
90
secondary structure
helix
92
97
secondary structure
beta
108
114
secondary structure
beta
121
122
secondary structure
beta
125
128
secondary structure
beta
131
135
secondary structure
beta
137
137
pfam
PF00576.18
Transthyretin
28
137
The protein belongs to the 5-hydroxyisourate hydrolase (HIUase)/transthyretin protein family. Accordingly, the complex adopts a transthyterin-like fold (based on Pfam entry PF00576.18 and the publication PMID:16952372). Transthyretin was shown in calorimetrics experiments to follow two-state folding/binding kinetics with the emergence of structure being linked to oligomerization (PMID:11152276).
2h6u
3iwu
3iwv
3q1e
MF4110004
Oligomerization region of the general control protein GCN4
2b1f
X-ray
1.50
homotetramer (dimer of dimers)
Saccharomyces cerevisiae
16472744
Deng Y, Liu J, Zheng Q, Eliezer D, Kallenbach NR, Lu M
Antiparallel four-stranded coiled coil specified by a 3-3-1 hydrophobic heptad repeat.
Structure
2006
2
14
247-55
Coiled-coil sequences in proteins commonly share a seven-amino acid repeat with nonpolar side chains at the first (a) and fourth (d) positions. We investigate here the role of a 3-3-1 hydrophobic repeat containing nonpolar amino acids at the a, d, and g positions in determining the structures of coiled coils using mutants of the GCN4 leucine zipper dimerization domain. When three charged residues at the g positions in the parental sequence are replaced by nonpolar alanine or valine side chains, stable four-helix structures result. The X-ray crystal structures of the tetramers reveal antiparallel, four-stranded coiled coils in which the a, d, and g side chains interlock in a combination of knobs-into-knobs and knobs-into-holes packing. Interfacial interactions in a coiled coil can therefore be prescribed by hydrophobic-polar patterns beyond the canonical 3-4 heptad repeat. The results suggest that the conserved, charged residues at the g positions in the GCN4 leucine zipper can impart a negative design element to disfavor thermodynamically more stable, antiparallel tetramers.
GO:0003682
chromatin binding
GO:0001190
transcriptional activator activity, RNA polymerase II transcription factor binding
GO:0000978
RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0042802
identical protein binding
GO:0001135
transcription factor activity, RNA polymerase II transcription factor recruiting
GO:0001084
transcription factor activity, TFIID-class binding
GO:0000981
RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0010691
negative regulation of ribosomal protein gene transcription from RNA polymerase II promoter in response to nutrient levels
GO:0006366
transcription from RNA polymerase II promoter
GO:1903833
positive regulation of cellular response to amino acid starvation
GO:0045899
positive regulation of RNA polymerase II transcriptional preinitiation complex assembly
GO:0001080
nitrogen catabolite activation of transcription from RNA polymerase II promoter
GO:0008652
cellular amino acid biosynthetic process
GO:0000790
nuclear chromatin
GO:0005667
transcription factor complex
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
1
Coils and zippers
Leucine zipper (tetrameric)
A
General control protein GCN4
Saccharomyces cerevisiae
MKVKQLEDAVEELLSANYHLENAVARLKKLVGER
34
P03069
249
281
11.7%
UniRef90_P03069
249
281
secondary structure
helix
250
278
pfam
PF07716.12
bZIP_2
224
276
B
General control protein GCN4
Saccharomyces cerevisiae
MKVKQLEDAVEELLSANYHLENAVARLKKLVGER
34
P03069
249
281
11.7%
UniRef90_P03069
249
281
secondary structure
helix
250
278
pfam
PF07716.12
bZIP_2
224
276
C
General control protein GCN4
Saccharomyces cerevisiae
MKVKQLEDAVEELLSANYHLENAVARLKKLVGER
34
P03069
249
281
11.7%
UniRef90_P03069
249
281
secondary structure
helix
250
278
pfam
PF07716.12
bZIP_2
224
276
D
General control protein GCN4
Saccharomyces cerevisiae
MKVKQLEDAVEELLSANYHLENAVARLKKLVGER
34
P03069
249
281
11.7%
UniRef90_P03069
249
281
secondary structure
helix
251
277
pfam
PF07716.12
bZIP_2
224
276
The subunits in the structure are bound via coiled coil interactions. Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure. Leucine zippers, phenylalanine zippers and alanine zippers are subclasses of coiled coils where the hydrophobic interactions between subunits are predominantly formed by leucine, phenylalanine or alanine residues, respectively. In the specific case of GCN4 refolding studies have explicitly shown that structure formation and dimerization happens at the same time (PMID:7548036)
A
The 225-281 region described in DisProt entry DP00083 covers 100% of the sequence present in the structure.
B
The 225-281 region described in DisProt entry DP00083 covers 100% of the sequence present in the structure.
C
The 225-281 region described in DisProt entry DP00083 covers 100% of the sequence present in the structure.
D
The 225-281 region described in DisProt entry DP00083 covers 100% of the sequence present in the structure.
1ce9
1dgc
1env
1fav
1fmh
1gcl
1gcm
1gk6
1gzl
1ihq
1ij0
1ij1
1ij2
1ij3
1kql
1ld4
1llm
1piq
1rb4
1rb5
1rb6
1swi
1tmz
1unt
1unu
1unv
1unw
1unx
1uny
1unz
1uo0
1uo1
1uo2
1uo3
1uo4
1uo5
1w5g
1w5h
1w5i
1w5j
1w5k
1w5l
1ysa
1zii
1zij
1zik
1zil
1zim
1zta
2ahp
2b22
2bni
2cce
2ccf
2ccn
2dgc
2g9j
2hy6
2ipz
2k8x
2n9b
2nrn
2o7h
2ovn
2vky
2vnl
2wg5
2wg6
2wpy
2wpz
2wq0
2wq1
2wq2
2wq3
2yny
2ynz
2yo0
2yo1
2yo2
2yo3
2zta
3azd
3ck4
3crp
3g9r
3gjp
3i1g
3i5c
3k7z
3p8m
3zmf
4c46
4dmd
4g2k
4hu5
4hu6
4niz
4nj0
4nj1
4nj2
4owi
4tl1
5apq
5aps
5apt
5apu
5apv
5apw
5apx
5apy
5iew
5iir
5iiv
MF2120014
Regulatory protein Rop
2ijk
X-ray
1.55
homodimer
Escherichia coli
18260113
Struble EB, Ladner JE, Brabazon DM, Marino JP
New crystal structures of ColE1 Rom and variants resulting from mutation of a surface exposed residue: Implications for RNA-recognition.
Proteins
2008
2
72
761-8
In ColE1, the plasmid encoded RNA one modulator (Rom) protein, which is also referred to as Rop, specifically binds and stabilizes an intermediate RNA loop-loop kissing structure formed between the plasmid encoded transcripts RNA I and RNA II and thereby acts as an auxiliary repressor of replication. Rom folds into a homodimeric, cylindrically packed four helix bundle with an exact twofold symmetry axis (Banner et al., J Mol Biol 1987;196:657-675; Eberle et al., J Biomol 1991;1:71-83). Previous studies (Castagnoli et al., EMBO J 1989;8:621-629; Predki et al., Cell 1995;80:41-50) have localized the RNA binding surface to the H1/H1' face of the helical bundle and found Phe14 to be a key determinant of the binding affinity and specificity for RNA kissing complexes. To investigate the role of Phe14 in RNA recognition, we have determined high-resolution crystal structures of two point mutants of Rom (F14Y and F14W), as well as a high-resolution structure of a crystal form of Rom in which the dimer comprises the asymmetric unit. Although the structures of F14Y and F14W share a very high degree of structural identity with that of the wild-type protein and each other, differences are observed between the three polypeptide chains found in the asymmetric unit of each crystal in the packing of the tryptophan and tyrosine side chains at position 14, as well as some of the other surface exposed side chains of key amino acids involved in RNA binding. In both the wild-type Rom and mutant structures, crystal packing forces can break the exact twofold symmetry of the dimer and influence the conformation of the side chains presented on the H1/H1' face of Rom. Since the new structures show such a high degree of structural identity, the disruption in RNA binding observed for the mutant proteins can be attributed specifically to the chemical nature of the side chain at position 14. Moreover, the fact that even subtle changes in the side chain at position 14 cannot be compensated for by the apparent flexibility of this side chain suggests a highly constrained packing of this residue in the RNA-protein complex.
GO:0006355
regulation of transcription, DNA-templated
GO:0006351
transcription, DNA-templated
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Coils and zippers
Coiled coil (dimeric, forming a 4-helix bundle)
A
Regulatory protein rop
Escherichia coli
GTKQEKTALNMARFIRSQTLTLLEKLNELDADEQADICESLHDHADELYRSCLARFGDDGENL
63
P03051
1
63
100%
UniRef90_P03051
2
63
secondary structure
helix
3
28
secondary structure
helix
32
56
pfam
PF01815.13
Rop
1
57
B
Regulatory protein rop
Escherichia coli
GTKQEKTALNMARFIRSQTLTLLEKLNELDADEQADICESLHDHADELYRSCLARFGDDGENL
63
P03051
1
63
100%
UniRef90_P03051
2
63
secondary structure
helix
2
28
secondary structure
helix
32
56
pfam
PF01815.13
Rop
1
57
Detailed thermodynamic and spectroscopic studies were carried out on the ColE1-ROP protein in order to establish a quantitative basis for the contribution of noncovalent interactions to the stability of four-helix-bundle proteins. The energetics of both heat- and GdnHCl-induced denaturation were measured by differential scanning microcalorimetry (DSC) and/or by following the change in circular dichroism in the far-UV range. No intermediate species could be detected during thermal unfolding of the dimer in the absence of GdnHCl. Under these conditions ROP unfolding exhibits a strict two-state behavior (PMID:8471599).
1b6q
4do2
1f4m
1f4n
2ghy
1gto
2ijh
2iji
2ijj
1qx8
1rpr
1gmg
3k79
1nkd
1rop
1rpo
1yo7
MF4100002
Bcr-Abl oncoprotein oligomerization domain
1k1f
X-ray
2.20
homotetramer (dimer of dimers)
Homo sapiens
11780146
Zhao X, Ghaffari S, Lodish H, Malashkevich VN, Kim PS
Structure of the Bcr-Abl oncoprotein oligomerization domain.
Nat. Struct. Biol.
2002
2
9
117-20
The Bcr-Abl oncoprotein is responsible for a wide range of human leukemias, including most cases of Philadelphia chromosome-positive chronic myelogenous leukemia. Oligomerization of Bcr-Abl is essential for oncogenicity. We determined the crystal structure of the N-terminal oligomerization domain of Bcr-Abl (residues 1-72 or Bcr1-72) and found a novel mode of oligomer formation. Two N-shaped monomers dimerize by swapping N-terminal helices and by forming an antiparallel coiled coil between C-terminal helices. Two dimers then stack onto each other to form a tetramer. The Bcr1-72 structure provides a basis for the design of inhibitors of Bcr-Abl transforming activity by disrupting Bcr-Abl oligomerization.
GO:0005524
ATP binding
GO:0005089
Rho guanyl-nucleotide exchange factor activity
GO:0004713
protein tyrosine kinase activity
GO:0019899
enzyme binding
GO:0004674
protein serine/threonine kinase activity
GO:0005096
GTPase activator activity
GO:0048008
platelet-derived growth factor receptor signaling pathway
GO:0051726
regulation of cell cycle
GO:0060313
negative regulation of blood vessel remodeling
GO:0043114
regulation of vascular permeability
GO:0043547
positive regulation of GTPase activity
GO:0050728
negative regulation of inflammatory response
GO:0007420
brain development
GO:0050885
neuromuscular process controlling balance
GO:0046777
protein autophosphorylation
GO:0002692
negative regulation of cellular extravasation
GO:0043314
negative regulation of neutrophil degranulation
GO:0030036
actin cytoskeleton organization
GO:0042472
inner ear morphogenesis
GO:0032496
response to lipopolysaccharide
GO:0018108
peptidyl-tyrosine phosphorylation
GO:0050766
positive regulation of phagocytosis
GO:0035556
intracellular signal transduction
GO:0035023
regulation of Rho protein signal transduction
GO:0030054
cell junction
GO:0045211
postsynaptic membrane
GO:0070062
extracellular exosome
GO:0014069
postsynaptic density
GO:0005829
cytosol
GO:0043234
protein complex
Chains E, F, G and H were removed as chains A, B, C and D represent the biologically relevant tetramer.
4
1
Coils and zippers
Coiled coil (tetrameric)
A
Breakpoint cluster region protein
Homo sapiens
MVDPVGFAEAWKAQFPDSEPPRMELRSVGDIEQELERAKASIRRLEQEVNQERFRMIYLQTLLAKEKKSYDR
72
P11274
1
72
5.7%
UniRef90_P11274
1
72
secondary structure
helix
5
15
secondary structure
helix
30
55
secondary structure
helix
57
67
pfam
PF09036.7
Bcr-Abl_Oligo
3
75
B
Breakpoint cluster region protein
Homo sapiens
MVDPVGFAEAWKAQFPDSEPPRMELRSVGDIEQELERAKASIRRLEQEVNQERFRMIYLQTLLAKEKKSYDR
72
P11274
1
72
5.7%
UniRef90_P11274
1
72
secondary structure
helix
7
13
secondary structure
helix
30
55
secondary structure
helix
57
67
pfam
PF09036.7
Bcr-Abl_Oligo
3
75
C
Breakpoint cluster region protein
Homo sapiens
MVDPVGFAEAWKAQFPDSEPPRMELRSVGDIEQELERAKASIRRLEQEVNQERFRMIYLQTLLAKEKKSYDR
72
P11274
1
72
5.7%
UniRef90_P11274
1
72
secondary structure
helix
6
15
secondary structure
helix
30
55
secondary structure
helix
57
67
pfam
PF09036.7
Bcr-Abl_Oligo
3
75
D
Breakpoint cluster region protein
Homo sapiens
MVDPVGFAEAWKAQFPDSEPPRMELRSVGDIEQELERAKASIRRLEQEVNQERFRMIYLQTLLAKEKKSYDR
72
P11274
1
72
5.7%
UniRef90_P11274
1
72
secondary structure
beta
4
4
secondary structure
helix
5
15
secondary structure
helix
30
55
secondary structure
helix
57
66
pfam
PF09036.7
Bcr-Abl_Oligo
3
75
The subunits in the structure are bound via coiled coil interactions (PMID:11780146). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
MF2120015
Antitoxin phd dimer (Escherichia coli)
3hry
X-ray
2.25
homodimer
Escherichia coli
20603017
Garcia-Pino A, Balasubramanian S, Wyns L, Gazit E, De Greve H, Magnuson RD, Charlier D, van Nuland NA, Loris R
Allostery and intrinsic disorder mediate transcription regulation by conditional cooperativity.
Cell
2010
1
142
101-11
Regulation of the phd/doc toxin-antitoxin operon involves the toxin Doc as co- or derepressor depending on the ratio between Phd and Doc, a phenomenon known as conditional cooperativity. The mechanism underlying this observed behavior is not understood. Here we show that monomeric Doc engages two Phd dimers on two unrelated binding sites. The binding of Doc to the intrinsically disordered C-terminal domain of Phd structures its N-terminal DNA-binding domain, illustrating allosteric coupling between highly disordered and highly unstable domains. This allosteric effect also couples Doc neutralization to the conditional regulation of transcription. In this way, higher levels of Doc tighten repression up to a point where the accumulation of toxin triggers the production of Phd to counteract its action. Our experiments provide the basis for understanding the mechanism of conditional cooperative regulation of transcription typical of toxin-antitoxin modules. This model may be applicable for the regulation of other biological systems.
Chain C was removed as chains A and B represent the biologically relevant dimer.
2
1
Other
Phd antitoxin
A
Phd protein
Escherichia coli
MQSINFRTARGNLSEVLNNVEAGEEVEITRRGREPAVIVSKATFEAYKKAALDAEFASLFDTLDSTNKELVNR
73
Q79A04
1
73
100%
UniRef90_Q06253
1
73
secondary structure
beta
3
5
secondary structure
helix
6
20
secondary structure
beta
26
29
secondary structure
beta
36
40
secondary structure
helix
41
49
pfam
PF02604.16
PhdYeFM_antitox
1
70
B
Phd protein
Escherichia coli
MQSINFRTARGNLSEVLNNVEAGEEVEITRRGREPAVIVSKATFEAYKKAALDAEFASLFDTLDSTNKELVNR
73
Q79A04
1
73
100%
UniRef90_Q06253
1
73
secondary structure
beta
3
5
secondary structure
helix
6
10
secondary structure
helix
13
20
secondary structure
beta
26
30
secondary structure
beta
33
33
secondary structure
beta
36
40
secondary structure
helix
41
48
pfam
PF02604.16
PhdYeFM_antitox
1
70
The dimerization of the prevents host death (phd) antitoxin from Escherichia virus P1 has been shown with differential scanning calorimetry to fit well to a two-state model consisting of a dimer unfolding into monomer species (PMID:20603017).
A
The 1-73 region described in DisProt entry DP00288 covers 100% of the sequence present in the structure.
B
The 1-73 region described in DisProt entry DP00288 covers 100% of the sequence present in the structure.
MF4120006
Cell division factor ZapA (Pseudomonas aeruginosa)
1t3u
X-ray
2.50
homotetramer
Pseudomonas aeruginosa
Rajashankar, K.R., Kneiwel, R., Solorzano, V., Lima, C.D.
Structure of a conserved hypothetical protein Pseudomonas aeruginosa PA01
To be published
-
GO:0007049
cell cycle
GO:0051301
cell division
GO:0005737
cytoplasm
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
1
Coils and zippers
Coiled coil (tetrameric)
A
Cell division protein ZapA
Pseudomonas aeruginosa
MSQSNTLTVQILDKEYCINCPDDERANLESAARYLDGKMREIRSSGKVIGADRVAVMAALNITHDLLHRKERLDQESSSTRERVRELLDRVDRALANPADAGEA
104
Q9HTW3
1
104
100%
UniRef90_Q9HTW3
1
104
secondary structure
beta
7
11
secondary structure
beta
14
18
secondary structure
helix
25
38
secondary structure
helix
40
44
secondary structure
helix
52
56
secondary structure
helix
58
97
pfam
PF05164.10
ZapA
7
97
B
Cell division protein ZapA
Pseudomonas aeruginosa
MSQSNTLTVQILDKEYCINCPDDERANLESAARYLDGKMREIRSSGKVIGADRVAVMAALNITHDLLHRKERLDQESSSTRERVRELLDRVDRALANPADAGEA
104
Q9HTW3
1
104
100%
UniRef90_Q9HTW3
1
104
secondary structure
beta
5
11
secondary structure
beta
14
20
secondary structure
helix
22
38
secondary structure
helix
40
44
secondary structure
helix
52
56
secondary structure
helix
58
92
pfam
PF05164.10
ZapA
7
97
C
Cell division protein ZapA
Pseudomonas aeruginosa
MSQSNTLTVQILDKEYCINCPDDERANLESAARYLDGKMREIRSSGKVIGADRVAVMAALNITHDLLHRKERLDQESSSTRERVRELLDRVDRALANPADAGEA
104
Q9HTW3
1
104
100%
UniRef90_Q9HTW3
1
104
secondary structure
beta
7
10
secondary structure
beta
15
18
secondary structure
helix
22
38
secondary structure
helix
40
44
secondary structure
helix
52
56
secondary structure
helix
58
97
pfam
PF05164.10
ZapA
7
97
D
Cell division protein ZapA
Pseudomonas aeruginosa
MSQSNTLTVQILDKEYCINCPDDERANLESAARYLDGKMREIRSSGKVIGADRVAVMAALNITHDLLHRKERLDQESSSTRERVRELLDRVDRALANPADAGEA
104
Q9HTW3
1
104
100%
UniRef90_Q9HTW3
1
104
secondary structure
beta
7
11
secondary structure
beta
14
18
secondary structure
helix
22
38
secondary structure
helix
40
45
secondary structure
helix
52
56
secondary structure
helix
58
94
pfam
PF05164.10
ZapA
7
97
The subunits in the structure are bound via coiled coil interactions as evidenced by the presence of a ZapA domain (Pfam PF05164.10, PMID:25002581). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
1w2e
MF2120016
Putative antitoxin phd dimer (Nitrosomonas europaea)
2odk
X-ray
1.40
homodimer
Nitrosomonas europaea
Osipiuk, J., Skarina, T., Kagan, O., Savchenko, A., Edwards, A., Joachimiak, A.
Crsytal structure of putative prevent-host-death protein from Nitrosomonas europaea.
To be published
-
Chains C and D were removed as chains A and B represent the biologically relevant dimer.
2
1
Other
Phd antitoxin
A
Uncharacterized protein
Nitrosomonas europaea
GHMHVWPVQDAKARFSEFLDACITEGPQIVSRRGAEEAVLVPIGEWRRLQAAARPSLKQLLLSDSARTEMLVPERGKARRRQVEPLRGS
89
Q82T22
1
85
100%
UniRef90_Q82T22
1
85
secondary structure
beta
4
6
secondary structure
helix
7
12
secondary structure
helix
14
23
secondary structure
beta
27
31
secondary structure
beta
34
41
secondary structure
helix
42
51
pfam
PF02604.16
PhdYeFM_antitox
1
74
B
Uncharacterized protein
Nitrosomonas europaea
GHMHVWPVQDAKARFSEFLDACITEGPQIVSRRGAEEAVLVPIGEWRRLQAAARPSLKQLLLSDSARTEMLVPERGKARRRQVEPLRGS
89
Q82T22
1
85
100%
UniRef90_Q82T22
1
85
secondary structure
beta
3
5
secondary structure
helix
6
11
secondary structure
helix
13
23
secondary structure
beta
26
30
secondary structure
beta
33
40
secondary structure
helix
41
50
pfam
PF02604.16
PhdYeFM_antitox
1
74
The dimerization of the prevents host death (phd) antitoxin from Escherichia virus P1 has been shown with differential scanning calorimetry to fit well to a two-state model consisting of a dimer unfolding into monomer species (PMID:20603017).
A
A homologue sharing the same Pfam domain (PF02604.16) has been experimentally characterized as disordered in DisProt entry DP00288.
B
A homologue sharing the same Pfam domain (PF02604.16) has been experimentally characterized as disordered in DisProt entry DP00288.
MF4140002
Tetramerization domain of the Mnt repressor
1qey
NMR
homotetramer
Enterobacteria phage P22
10426954
Nooren IM, Kaptein R, Sauer RT, Boelens R
The tetramerization domain of the Mnt repressor consists of two right-handed coiled coils.
Nat. Struct. Biol.
1999
8
6
755-9
The tetrameric Mnt repressor is involved in the genetic switch between the lysogenic and lytic growth of Salmonella bacteriophage P22. The solution structure of its C-terminal tetramerization domain, which holds together the two dimeric DNA-binding domains, has been determined by NMR spectroscopy. This structure reveals an assembly of four alpha-helical subunits, consisting of a dimer of two antiparallel coiled coils with a unique right-handed twist. The superhelical winding is considerably stronger and the interhelical separation closer than those found in the well-known left-handed coiled coils in fibrous proteins and leucine zippers. An unusual asymmetry arises between the two monomers that comprise one right-handed coiled coil. A difference in the packing to the adjacent monomer of the other coiled coil occurs with an offset of two helical turns. The two asymmetric monomers within each coiled coil interconvert on a time scale of seconds. Both with respect to symmetry and handedness of helical packing, the C2 symmetric four-helix bundle of Mnt differs from other oligomerization domains that assemble DNA-binding modules, such as that in the tumor suppressor p53 and the E. coli lac repressor.
GO:0003677
DNA binding
GO:0006355
regulation of transcription, DNA-templated
GO:0006351
transcription, DNA-templated
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
1
Coils and zippers
Coiled coil (tetrameric)
A
Regulatory protein mnt
Enterobacteria phage P22
RNDAERLADEQSELVKKMVFDTLKDLYKKTT
31
P03049
53
83
37.3%
UniRef90_P03049
53
83
secondary structure
helix
55
82
pfam
PF11423.5
Repressor_Mnt
53
80
B
Regulatory protein mnt
Enterobacteria phage P22
RNDAERLADEQSELVKKMVFDTLKDLYKKTT
31
P03049
53
83
37.3%
UniRef90_P03049
53
83
secondary structure
helix
55
80
pfam
PF11423.5
Repressor_Mnt
53
80
C
Regulatory protein mnt
Enterobacteria phage P22
RNDAERLADEQSELVKKMVFDTLKDLYKKTT
31
P03049
53
83
37.3%
UniRef90_P03049
53
83
secondary structure
helix
55
82
pfam
PF11423.5
Repressor_Mnt
53
80
D
Regulatory protein mnt
Enterobacteria phage P22
RNDAERLADEQSELVKKMVFDTLKDLYKKTT
31
P03049
53
83
37.3%
UniRef90_P03049
53
83
secondary structure
helix
55
80
pfam
PF11423.5
Repressor_Mnt
53
80
The subunits in the structure are bound via coiled coil interactions (PMID:10426954). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
MF2100005
ING4 dimerization domain
4afl
X-ray
2.28
homodimer
Homo sapiens
22334692
Culurgioni S, Munoz IG, Moreno A, Palacios A, Villate M, Palmero I, Montoya G, Blanco FJ
The crystal structure of the inhibitor of growth 4 (ING4) dimerization domain reveals the functional organization of the ING family of chromatin binding proteins.
J. Biol. Chem.
2012
The protein ING4 binds to histone H3 trimethylated at Lys4 (H3K4me3) through its C-terminal PlantHomeoDomain (PHD), thus recruiting the HBO1 histone acetyltransferase complex to target promoters. The structure of the PHD finger bound to an H3K4me3 peptide has been described, as well as the disorder and flexibility in the ING4 central region. We report the crystal structure of the ING4 N-terminal domain, which shows an antiparallel coiled-coil homodimer with each protomer folded into a helix-loop-helix structure. This arrangement suggests that ING4 can bind simultaneously two histone tails, on the same or different nucleosomes. Dimerization has a direct impact on ING4 tumor suppressor activity since monomeric mutants lose the ability of inducing apoptosis after genotoxic stress. Homology modeling based on the ING4 structure suggests that other ING dimers may also exist.
GO:0035064
methylated histone binding
GO:0008270
zinc ion binding
GO:0003713
transcription coactivator activity
GO:0043982
histone H4-K8 acetylation
GO:0006978
DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator
GO:0008285
negative regulation of cell proliferation
GO:0006260
DNA replication
GO:0006915
apoptotic process
GO:0043983
histone H4-K12 acetylation
GO:0043065
positive regulation of apoptotic process
GO:0043981
histone H4-K5 acetylation
GO:0043966
histone H3 acetylation
GO:0007050
cell cycle arrest
GO:0045892
negative regulation of transcription, DNA-templated
GO:0045926
negative regulation of growth
GO:0000123
histone acetyltransferase complex
Chains B, D, E and F were removed as chains A and C represent the biologically relevant dimer.
2
1
Coils and zippers
Coiled coil (dimeric, forming a 4-helix bundle)
A
Inhibitor of growth protein 4
Homo sapiens
AAGMYLEHYLDSIENLPFELQRNFQLMRDLDQRTEDLKAEIDKLATEYMSSARSLSSEEKLALLKQIQEAYGKCKEFGDDKVQLAMQTYEMVDKHIRRLDTDLA
104
Q9UNL4
2
105
41.8%
UniRef90_Q9UNL4
2
105
secondary structure
helix
6
13
secondary structure
helix
15
27
secondary structure
helix
29
49
secondary structure
helix
51
53
secondary structure
helix
61
86
secondary structure
helix
88
91
secondary structure
helix
93
104
pfam
PF12998.4
ING
6
107
C
Inhibitor of growth protein 4
Homo sapiens
AAGMYLEHYLDSIENLPFELQRNFQLMRDLDQRTEDLKAEIDKLATEYMSSARSLSSEEKLALLKQIQEAYGKCKEFGDDKVQLAMQTYEMVDKHIRRLDTDLA
104
Q9UNL4
2
105
41.8%
UniRef90_Q9UNL4
2
105
secondary structure
helix
6
13
secondary structure
helix
15
27
secondary structure
helix
29
49
secondary structure
helix
51
55
secondary structure
helix
61
86
secondary structure
helix
88
91
secondary structure
helix
93
105
pfam
PF12998.4
ING
6
107
The subunits in the structure are bound via coiled coil interactions (PMID:22334692). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
MF2201005
H2A-H2B histone dimer (human/mouse), containing histone variants macro-H2A.1 and H2B type 3-A
1u35
X-ray
3.00
heterodimer
Homo sapiens / Mus musculus
16107708
Chakravarthy S, Gundimella SK, Caron C, Perche PY, Pehrson JR, Khochbin S, Luger K
Structural characterization of the histone variant macroH2A.
Mol. Cell. Biol.
2005
17
25
7616-24
macroH2A is an H2A variant with a highly unusual structural organization. It has a C-terminal domain connected to the N-terminal histone domain by a linker. Crystallographic and biochemical studies show that changes in the L1 loop in the histone fold region of macroH2A impact the structure and potentially the function of nucleosomes. The 1.6-A X-ray structure of the nonhistone region reveals an alpha/beta fold which has previously been found in a functionally diverse group of proteins. This region associates with histone deacetylases and affects the acetylation status of nucleosomes containing macroH2A. Thus, the unusual domain structure of macroH2A integrates independent functions that are instrumental in establishing a structurally and functionally unique chromatin domain.
GO:0003677
DNA binding
GO:0046982
protein heterodimerization activity
GO:0006334
nucleosome assembly
GO:0070062
extracellular exosome
GO:0000786
nucleosome
GO:0005634
nucleus
Chains A, B, E, F, G, H, I and J have been removed to highlight the basic interaction that forms the histone dimer composed of chains C and D.
2
2
Histone-like interactions
Histones
C
Core histone macro-H2A.1
Homo sapiens
MSSRGGKKKSTKTSRSAKAGVIFPVGRMLRYIKKGHPKYRIGVGAPVYMAAVLEYLTAEILELAVNAARDNKKGRVTPRHILLAVANDEELNQLLKGVTIASGGVLPNIHPELLAKKRGS
120
O75367
1
120
32.3%
UniRef90_O75367
1
120
secondary structure
helix
15
19
secondary structure
helix
25
35
secondary structure
beta
40
41
secondary structure
helix
45
70
secondary structure
beta
75
76
secondary structure
helix
78
87
secondary structure
helix
89
94
secondary structure
helix
111
113
pfam
PF00125.21
Histone
2
88
pfam
PF16211.2
Histone_H2A_C
89
123
D
Histone H2B type 3-A
Mus musculus
MPEPSRSTPAPKKGSKKAITKAQKKDGKKRKRGRKESYSIYVYKVLKQVHPDTGISSKAMGIMNSFVNDIFERIASEASRLAHYNKRSTITSREVQTAVRLLLPGELAKHAVSEGTKAVTKYTSSK
126
Q9D2U9
1
126
100%
UniRef90_Q9D2U9
1
126
secondary structure
helix
39
49
secondary structure
beta
54
55
secondary structure
helix
57
84
secondary structure
beta
89
90
secondary structure
helix
92
102
secondary structure
helix
105
122
pfam
PF00125.21
Histone
2
102
Histones form parts of the nucleosome particle by dimerization and subsequent multimerization (PMID:1946434). The dimer contains both histone subunits in a highly intertwined conformation reflecting the possible domain-swapped origins of the structure (PMID:17391511). Accordingly, this dimerization has been experimentally characterized to be coupled to the structure formation of both interacting partners (PMID:12779337); this synergistic folding has been shown separately for H2A-H2B dimers (PMID:15588829) and H3-H4 dimers as well (PMID:15096635). Histones containing various types of monomeric subunits can exhibit varying stability and folding kinetics. E.g. in the case of H3-H4 histones, the dimerization is a complex process with the two monomers first adopting an intermediate state upon encounter and then reaching the classical histone fold through restructurization (PMID:12779337). However, independent of composition and folding kinetics, all histones appear to fold in a cooperative fashion that is coupled to binding (PMID:11669650).
MF2201006
H2A-H2B histone dimer (human/Xenopus laevis), containing histone variants macro-H2A.1 and H2B 1.1
2f8n
X-ray
2.90
heterodimer
Homo sapiens / Xenopus laevis
Chakravarthy, S., Luger, K.
Nucleosomes containing the histone domain of macroH2A: In vitro possibilities.
To be published
-
GO:0003677
DNA binding
GO:0046982
protein heterodimerization activity
GO:0005634
nucleus
GO:0000786
nucleosome
Chains A, B, D, E, F, I, J and K have been removed to highlight the basic interaction that forms the histone dimer composed of chains G and H.
2
2
Histone-like interactions
Histones
G
Core histone macro-H2A.1
Homo sapiens
MSSRGGKKKSTKTSRSAKAGVIFPVGRMLRYIKKGHPKYRIGVGAPVYMAAVLEYLTAEILELAVNAARDNKKGRVTPRHILLAVANDEELNQLLKGVTIASGGVLPNIHPELLAKKRGS
120
O75367
1
120
32.3%
UniRef90_O75367
1
120
secondary structure
helix
15
19
secondary structure
helix
25
35
secondary structure
beta
40
41
secondary structure
helix
44
70
secondary structure
beta
75
76
secondary structure
helix
78
86
secondary structure
helix
89
94
secondary structure
helix
111
113
pfam
PF00125.21
Histone
2
88
pfam
PF16211.2
Histone_H2A_C
89
123
H
Histone H2B 1.1
Xenopus laevis
MAKSAPAPKKGSKKAVTKTQKKDGKKRRKTRKESYAIYVYKVLKQVHPDTGISSKAMSIMNSFVNDVFERIAGEASRLAHYNKRSTITSREIQTAVRLLLPGELAKHAVSEGTKAVTKYTSAK
123
P02281
4
126
97.6%
UniRef90_P57053
5
126
secondary structure
helix
39
47
secondary structure
beta
54
55
secondary structure
helix
57
84
secondary structure
beta
89
90
secondary structure
helix
92
102
secondary structure
helix
105
123
pfam
PF00125.21
Histone
2
102
Histones form parts of the nucleosome particle by dimerization and subsequent multimerization (PMID:1946434). The dimer contains both histone subunits in a highly intertwined conformation reflecting the possible domain-swapped origins of the structure (PMID:17391511). Accordingly, this dimerization has been experimentally characterized to be coupled to the structure formation of both interacting partners (PMID:12779337); this synergistic folding has been shown separately for H2A-H2B dimers (PMID:15588829) and H3-H4 dimers as well (PMID:15096635). Histones containing various types of monomeric subunits can exhibit varying stability and folding kinetics. E.g. in the case of H3-H4 histones, the dimerization is a complex process with the two monomers first adopting an intermediate state upon encounter and then reaching the classical histone fold through restructurization (PMID:12779337). However, independent of composition and folding kinetics, all histones appear to fold in a cooperative fashion that is coupled to binding (PMID:11669650).
MF2211001
H2A-H2B histone dimer (human/Xenopus laevis), containing histone variants H2A.Z and H2B 1.1
1f66
X-ray
2.60
heterodimer
Mus musculus / Xenopus laevis
11101893
Suto RK, Clarkson MJ, Tremethick DJ, Luger K
Crystal structure of a nucleosome core particle containing the variant histone H2A.Z.
Nat. Struct. Biol.
2000
12
7
1121-4
Activation of transcription within chromatin has been correlated with the incorporation of the essential histone variant H2A.Z into nucleosomes. H2A.Z and other histone variants may establish structurally distinct chromosomal domains; however, the molecular mechanism by which they function is largely unknown. Here we report the 2.6 A crystal structure of a nucleosome core particle containing the histone variant H2A.Z. The overall structure is similar to that of the previously reported 2.8 A nucleosome structure containing major histone proteins. However, distinct localized changes result in the subtle destabilization of the interaction between the (H2A.Z-H2B) dimer and the (H3-H4)(2) tetramer. Moreover, H2A.Z nucleosomes have an altered surface that includes a metal ion. This altered surface may lead to changes in higher order structure, and/or could result in the association of specific nuclear proteins with H2A.Z. Finally, incorporation of H2A.Z and H2A within the same nucleosome is unlikely, due to significant changes in the interface between the two H2A.Z-H2B dimers.
GO:0046982
protein heterodimerization activity
GO:0003677
DNA binding
GO:0005634
nucleus
GO:0000786
nucleosome
Chains A, B, E, F, G, H, I and J have been removed to highlight the basic interaction that forms the histone dimer composed of chains C and D.
2
2
Histone-like interactions
Histones
C
Histone H2A.Z
Mus musculus
MAGGKAGKDSGKAKTKAVSRSQRAGLQFPVGRIHRHLKSRTTSHGRVGATAAVYSAAILEYLTAEVLELAGNASKDLKVKRITPRHLQLAIRGDEELDSLIKATIAGGGVIPHIHKSLIGKKGQQKTV
128
P0C0S6
1
128
100%
UniRef90_P0C0S5
1
128
secondary structure
helix
20
24
secondary structure
helix
30
39
secondary structure
beta
46
47
secondary structure
helix
51
75
secondary structure
beta
81
82
secondary structure
helix
84
93
secondary structure
helix
95
100
secondary structure
helix
116
118
pfam
PF00125.21
Histone
4
94
pfam
PF16211.2
Histone_H2A_C
95
127
D
Histone H2B 1.1
Xenopus laevis
MPEPAKSAPAPKKGSKKAVTKTQKKDGKKRRKTRKESYAIYVYKVLKQVHPDTGISSKAMSIMNSFVNDVFERIAGEASRLAHYNKRSTITSREIQTAVRLLLPGELAKHAVSEGTKAVTKYTSAK
126
P02281
1
126
100%
UniRef90_P57053
1
126
secondary structure
helix
39
49
secondary structure
beta
54
55
secondary structure
helix
57
84
secondary structure
beta
89
90
secondary structure
helix
92
102
secondary structure
helix
105
124
pfam
PF00125.21
Histone
2
102
Histones form parts of the nucleosome particle by dimerization and subsequent multimerization (PMID:1946434). The dimer contains both histone subunits in a highly intertwined conformation reflecting the possible domain-swapped origins of the structure (PMID:17391511). Accordingly, this dimerization has been experimentally characterized to be coupled to the structure formation of both interacting partners (PMID:12779337); this synergistic folding has been shown separately for H2A-H2B dimers (PMID:15588829) and H3-H4 dimers as well (PMID:15096635). Histones containing various types of monomeric subunits can exhibit varying stability and folding kinetics. E.g. in the case of H3-H4 histones, the dimerization is a complex process with the two monomers first adopting an intermediate state upon encounter and then reaching the classical histone fold through restructurization (PMID:12779337). However, independent of composition and folding kinetics, all histones appear to fold in a cooperative fashion that is coupled to binding (PMID:11669650).
MF2200003
H2A-H2B histone dimer (human), containing histone variants H2A.Z and H2B type 1-J
3wa9
X-ray
3.07
heterodimer
Homo sapiens
24311584
Horikoshi N, Sato K, Shimada K, Arimura Y, Osakabe A, Tachiwana H, Hayashi-Takanaka Y, Iwasaki W, Kagawa W, Harata M, Kimura H, Kurumizaka H
Structural polymorphism in the L1 loop regions of human H2A.Z.1 and H2A.Z.2.
Acta Crystallogr. D Biol. Crystallogr.
2013
Pt 12
69
2431-9
The histone H2A.Z variant is widely conserved among eukaryotes. Two isoforms, H2A.Z.1 and H2A.Z.2, have been identified in vertebrates and may have distinct functions in cell growth and gene expression. However, no structural differences between H2A.Z.1 and H2A.Z.2 have been reported. In the present study, the crystal structures of nucleosomes containing human H2A.Z.1 and H2A.Z.2 were determined. The structures of the L1 loop regions were found to clearly differ between H2A.Z.1 and H2A.Z.2, although their amino-acid sequences in this region are identical. This structural polymorphism may have been induced by a substitution that evolutionally occurred at the position of amino acid 38 and by the flexible nature of the L1 loops of H2A.Z.1 and H2A.Z.2. It was also found that in living cells nucleosomal H2A.Z.1 exchanges more rapidly than H2A.Z.2. A mutational analysis revealed that the amino-acid difference at position 38 is at least partially responsible for the distinctive dynamics of H2A.Z.1 and H2A.Z.2. These findings provide important new information for understanding the differences in the regulation and functions of H2A.Z.1 and H2A.Z.2 in cells.
GO:0046982
protein heterodimerization activity
GO:0003677
DNA binding
GO:0000786
nucleosome
GO:0005634
nucleus
Chains A, B, E, F, G, H, I and J have been removed to highlight the basic interaction that forms the histone dimer composed of chains C and D.
2
2
Histone-like interactions
Histones
C
Histone H2A.Z
Homo sapiens
GSHMAGGKAGKDSGKAKTKAVSRSQRAGLQFPVGRIHRHLKSRTTSHGRVGATAAVYSAAILEYLTAEVLELAGNASKDLKVKRITPRHLQLAIRGDEELDSLIKATIAGGGVIPHIHKSLIGKKGQQKTV
131
P0C0S5
1
128
100%
UniRef90_P0C0S5
1
128
secondary structure
helix
20
24
secondary structure
helix
30
38
secondary structure
beta
46
47
secondary structure
helix
51
76
secondary structure
beta
81
82
secondary structure
helix
84
93
secondary structure
helix
95
100
secondary structure
helix
116
118
pfam
PF00125.21
Histone
4
94
pfam
PF16211.2
Histone_H2A_C
95
127
D
Histone H2B type 1-J
Homo sapiens
GSHMPEPAKSAPAPKKGSKKAVTKAQKKDGKKRKRSRKESYSIYVYKVLKQVHPDTGISSKAMGIMNSFVNDIFERIAGEASRLAHYNKRSTITSREIQTAVRLLLPGELAKHAVSEGTKAVTKYTSAK
129
P06899
1
126
100%
UniRef90_P06899
1
126
secondary structure
helix
39
49
secondary structure
beta
54
55
secondary structure
helix
57
84
secondary structure
beta
89
90
secondary structure
helix
92
100
secondary structure
helix
105
123
pfam
PF00125.21
Histone
2
102
Histones form parts of the nucleosome particle by dimerization and subsequent multimerization (PMID:1946434). The dimer contains both histone subunits in a highly intertwined conformation reflecting the possible domain-swapped origins of the structure (PMID:17391511). Accordingly, this dimerization has been experimentally characterized to be coupled to the structure formation of both interacting partners (PMID:12779337); this synergistic folding has been shown separately for H2A-H2B dimers (PMID:15588829) and H3-H4 dimers as well (PMID:15096635). Histones containing various types of monomeric subunits can exhibit varying stability and folding kinetics. E.g. in the case of H3-H4 histones, the dimerization is a complex process with the two monomers first adopting an intermediate state upon encounter and then reaching the classical histone fold through restructurization (PMID:12779337). However, independent of composition and folding kinetics, all histones appear to fold in a cooperative fashion that is coupled to binding (PMID:11669650).
4cay
5b31
5fug
MF2210001
H2A-H2B histone dimer (Xenopus laevis), containing histone variants H2A type 1 and H2B 1.1
1aoi
X-ray
2.80
heterodimer
Xenopus laevis
9305837
Luger K, Mäder AW, Richmond RK, Sargent DF, Richmond TJ
Crystal structure of the nucleosome core particle at 2.8 A resolution.
Nature
1997
6648
389
251-60
The X-ray crystal structure of the nucleosome core particle of chromatin shows in atomic detail how the histone protein octamer is assembled and how 146 base pairs of DNA are organized into a superhelix around it. Both histone/histone and histone/DNA interactions depend on the histone fold domains and additional, well ordered structure elements extending from this motif. Histone amino-terminal tails pass over and between the gyres of the DNA superhelix to contact neighbouring particles. The lack of uniformity between multiple histone/DNA-binding sites causes the DNA to deviate from ideal superhelix geometry.
GO:0046982
protein heterodimerization activity
GO:0003677
DNA binding
GO:0005634
nucleus
GO:0000786
nucleosome
Chains A, B, E, F, G, H, I and J have been removed to highlight the basic interaction that forms the histone dimer composed of chains C and D.
2
2
Histone-like interactions
Histones
C
Histone H2A type 1
Xenopus laevis
GKQGGKTRAKAKTRSSRAGLQFPVGRVHRLLRKGNYAERVGAGAPVYLAAVLEYLTAEILELAGNAARDNKKTRIIPRHLQLAVRNDEELNKLLGRVTIAQGGVLPNIQSVLLPKK
116
P06897
5
120
89.2%
UniRef90_Q00728
6
120
secondary structure
helix
6
8
secondary structure
helix
18
22
secondary structure
helix
28
36
secondary structure
beta
43
44
secondary structure
helix
47
73
secondary structure
beta
78
79
secondary structure
helix
81
90
secondary structure
helix
92
97
secondary structure
helix
114
116
pfam
PF00125.21
Histone
2
91
D
Histone H2B 1.1
Xenopus laevis
KKRRKTRKESYAIYVYKVLKQVHPDTGISSKAMSIMNSFVNDVFERIAGEASRLAHYNKRSTITSREIQTAVRLLLPGELAKHAVSEGTKAVTKYTSAK
99
P02281
28
126
78.6%
UniRef90_P57053
28
126
secondary structure
helix
39
49
secondary structure
beta
54
55
secondary structure
helix
57
84
secondary structure
beta
89
90
secondary structure
helix
92
102
secondary structure
helix
105
123
pfam
PF00125.21
Histone
2
102
Histones form parts of the nucleosome particle by dimerization and subsequent multimerization (PMID:1946434). The dimer contains both histone subunits in a highly intertwined conformation reflecting the possible domain-swapped origins of the structure (PMID:17391511). Accordingly, this dimerization has been experimentally characterized to be coupled to the structure formation of both interacting partners (PMID:12779337); this synergistic folding has been shown separately for H2A-H2B dimers (PMID:15588829) and H3-H4 dimers as well (PMID:15096635). Histones containing various types of monomeric subunits can exhibit varying stability and folding kinetics. E.g. in the case of H3-H4 histones, the dimerization is a complex process with the two monomers first adopting an intermediate state upon encounter and then reaching the classical histone fold through restructurization (PMID:12779337). However, independent of composition and folding kinetics, all histones appear to fold in a cooperative fashion that is coupled to binding (PMID:11669650).
2fj7
4j8u
1kx3
1kx4
1kx5
1m18
1m19
1m1a
3o62
1p34
1p3a
1p3b
1p3f
1p3g
1p3i
1p3k
1p3l
1p3m
1p3o
1p3p
3reh
3rei
3rej
3rek
3rel
1s32
4wu8
4wu9
3b6f
3b6g
4j8v
4j8w
4j8x
4kgc
3kuy
3kwq
3kxb
3lel
3lja
3lz0
3lz1
3mgp
3mgq
3mgr
3mgs
3mnn
2nzd
3ut9
3uta
3utb
4xzq
4ys3
4z66
1zbb
1zla
3tu4
4ld9
4xuj
4zux
5cp6
5dnm
5dnn
5e5a
5f99
5g2e
5hq2
5nl0
5x0x
5x0y
MF2210002
H2A-H2B histone dimer (Gallus gallus), containing histone variants H2A-IV and H2B 5
2aro
X-ray
2.10
heterodimer
Gallus gallus
16920041
Wood CM, Sodngam S, Nicholson JM, Lambert SJ, Reynolds CD, Baldwin JP
The oxidised histone octamer does not form a H3 disulphide bond.
Biochim. Biophys. Acta
2006
8
1764
1356-62
A H3 dimer band is produced when purified native histone octamers are run on an SDS-PAGE gel in a beta-mercaptoethanol-free environment. To investigate this, native histone octamer crystals, derived from chicken erythrocytes, and of structure (H2A-H2B)-(H4-H3)-(H3'-H4')-(H2B'-H2A'), were grown in 2 M KCl, 1.35 M potassium phosphates and 250-350 microM of the oxidising agent S-nitrosoglutathione, pH 6.9. X-ray diffraction data were acquired to 2.10 A resolution, yielding a structure with an Rwork value of 18.6% and an Rfree of 22.5%. The space group is P6(5), the asymmetric unit of which contains one complete octamer. Compared to the 1.90 A resolution, unoxidised native histone octamer structure, the crystals show a reduction of 2.5% in the c-axis of the unit cell, and free-energy calculations reveal that the H3-H3' dimer interface in the latter has become thermodynamically stable, in contrast to the former. Although the inter-sulphur distance of the two H3 cysteines in the oxidised native histone octamer has reduced to 6 A from the 7 A of the unoxidised form, analysis of the hydrogen bonds that constitute the (H4-H3)-(H3'-H4') tetramer indicates that the formation of a disulphide bond in the H3-H3' dimer interface is incompatible with stable tetramer formation. The biochemical and biophysical evidence, taken as a whole, is indicative of crystals that have a stable H3-H3' dimer interface, possibly extending to the interface within an isolated H3-H3' dimer, observed in SDS-PAGE gels.
GO:0003677
DNA binding
GO:0046982
protein heterodimerization activity
GO:0000786
nucleosome
GO:0005634
nucleus
Chains C, D, E, F, G and H have been removed to highlight the basic interaction that forms the histone dimer composed of chains A and B.
2
2
Histone-like interactions
Histones
A
Histone H2A-IV
Gallus gallus
MSGRGKQGGKARAKAKSRSSRAGLQFPVGRVHRLLRKGNYAERVGAGAPVYLAAVLEYLTAEILELAGNAARDNKKTRIIPRHLQLAIRNDEELNKLLGKVTIAQGGVLPNIQAVLLPKKTDSHKAKAK
129
P02263
1
129
100%
UniRef90_P02263
1
129
secondary structure
helix
18
22
secondary structure
helix
28
37
secondary structure
beta
43
44
secondary structure
helix
47
72
secondary structure
beta
78
79
secondary structure
helix
81
89
secondary structure
helix
92
97
secondary structure
helix
114
116
pfam
PF00125.21
Histone
2
91
pfam
PF16211.2
Histone_H2A_C
92
126
B
Histone H2B 5
Gallus gallus
MPEPAKSAPAPKKGSKKAVTKTQKKGDKKRKKSRKESYSIYVYKVLKQVHPDTGISSKAMGIMNSFVNDIFERIAGEASRLAHYNKRSTITSREIQTAVRLLLPGELAKHAVSEGTKAVTKYTSSK
126
P0C1H4
1
126
100%
UniRef90_P0C1H4
1
126
secondary structure
helix
39
49
secondary structure
beta
54
55
secondary structure
helix
57
84
secondary structure
beta
89
90
secondary structure
helix
92
102
secondary structure
helix
105
124
pfam
PF00125.21
Histone
2
102
Histones form parts of the nucleosome particle by dimerization and subsequent multimerization (PMID:1946434). The dimer contains both histone subunits in a highly intertwined conformation reflecting the possible domain-swapped origins of the structure (PMID:17391511). Accordingly, this dimerization has been experimentally characterized to be coupled to the structure formation of both interacting partners (PMID:12779337); this synergistic folding has been shown separately for H2A-H2B dimers (PMID:15588829) and H3-H4 dimers as well (PMID:15096635). Histones containing various types of monomeric subunits can exhibit varying stability and folding kinetics. E.g. in the case of H3-H4 histones, the dimerization is a complex process with the two monomers first adopting an intermediate state upon encounter and then reaching the classical histone fold through restructurization (PMID:12779337). However, independent of composition and folding kinetics, all histones appear to fold in a cooperative fashion that is coupled to binding (PMID:11669650).
1eqz
1hio
2hio
1hq3
1tzy
MF2201007
H2A-H2B histone dimer (mouse/human), containing histone variants H2A and H2B type 1-B
3x1u
X-ray
3.25
heterodimer
Mus musculus / Homo sapiens
26188507
Padavattan S, Shinagawa T, Hasegawa K, Kumasaka T, Ishii S, Kumarevel T
Structural and functional analyses of nucleosome complexes with mouse histone variants TH2a and TH2b, involved in reprogramming.
Biochem. Biophys. Res. Commun.
2015
3
464
929-35
Histone variants TH2a and TH2b are highly expressed in testes, oocytes and zygotes. Our recent analysis suggested that these histone variants enhance the induced generation of pluripotent stem cells (iPSCs) when co-expressed along with four transcription factors, Oct3/4, Sox2, Klf4 and c-Myc (OSKM), and are associated with an open chromatin structure [1]. In the present study, we report the crystal structures of nucleosomes (NCPs) with the mouse histone variants, TH2a and TH2b. The structures revealed two significant changes, as compared to the canonical counterparts: fewer histone-DNA contacts and changes in dimer-dimer interactions between TH2a-TH2a' (L1-loop). In vivo studies with domain swapping and point mutants of the variants revealed that the residues in the histone tails and the TH2a-L1 loop are important for reprogramming. Taken together, our work indicates that the NCP variants with structural modifications and flexible tails are most likely important for enhanced reprogramming of functions.
GO:0003677
DNA binding
GO:0046982
protein heterodimerization activity
GO:0000786
nucleosome
GO:0000784
nuclear chromosome, telomeric region
Chains A, B, E, F, G, H, I and J have been removed to highlight the basic interaction that forms the histone dimer composed of chains C and D.
2
2
Histone-like interactions
Histones
C
Histone H2A
Mus musculus
SGPTKRGGKARAKVKSRSSRAGLQFPVGRVHRLLRQGNYAQRIGAGAPVYLAAVLEYLTAEVLELAGNAARDNKKTRITPRHLQLAIRNDEELNKLLGRVTIAQGGVLPNIQAVLLPKKTESHKSQTK
128
Q8CGP4
2
129
99.2%
UniRef90_Q93077
2
124
secondary structure
helix
18
21
secondary structure
helix
28
36
secondary structure
beta
43
44
secondary structure
helix
48
73
secondary structure
beta
78
79
secondary structure
helix
81
90
secondary structure
helix
93
97
secondary structure
helix
114
116
pfam
PF00125.21
Histone
2
91
pfam
PF16211.2
Histone_H2A_C
92
126
D
Histone H2B type 1-B
Homo sapiens
EPSKSAPAPKKGSKKAITKAQKKDGKKRKRSRKESYSIYVYKVLKQVHPDTGISSKAMGIMNSFVNDIFERIAGEASRLAHYNKRSTITSREIQTAVRLLLPGELAKHAVSEGTKAVTKYTSSK
124
P33778
3
126
98.4%
UniRef90_P33778
3
126
secondary structure
helix
39
49
secondary structure
beta
54
55
secondary structure
helix
57
84
secondary structure
beta
89
90
secondary structure
helix
92
102
secondary structure
helix
105
116
secondary structure
helix
119
123
pfam
PF00125.21
Histone
2
102
Histones form parts of the nucleosome particle by dimerization and subsequent multimerization (PMID:1946434). The dimer contains both histone subunits in a highly intertwined conformation reflecting the possible domain-swapped origins of the structure (PMID:17391511). Accordingly, this dimerization has been experimentally characterized to be coupled to the structure formation of both interacting partners (PMID:12779337); this synergistic folding has been shown separately for H2A-H2B dimers (PMID:15588829) and H3-H4 dimers as well (PMID:15096635). Histones containing various types of monomeric subunits can exhibit varying stability and folding kinetics. E.g. in the case of H3-H4 histones, the dimerization is a complex process with the two monomers first adopting an intermediate state upon encounter and then reaching the classical histone fold through restructurization (PMID:12779337). However, independent of composition and folding kinetics, all histones appear to fold in a cooperative fashion that is coupled to binding (PMID:11669650).
MF2210003
H2A-H2B histone dimer (Drosophila melanogaster)
2nqb
X-ray
2.30
heterodimer
Drosophila melanogaster
Chakravarthy, S., Luger, K.
Comparative analysis of nucleosome structures from different species.
To be published
-
GO:0003677
DNA binding
GO:0046982
protein heterodimerization activity
GO:0006334
nucleosome assembly
GO:0000788
nuclear nucleosome
GO:0005811
lipid particle
Chains A, B, E, F, G, H, I and J have been removed to highlight the basic interaction that forms the histone dimer composed of chains C and D.
2
2
Histone-like interactions
Histones
C
Histone H2A
Drosophila melanogaster
SGRGKGGKVKGKAKSRSNRAGLQFPVGRIHRLLRKGNYAERVGAGAPVYLAAVMEYLAAEVLELAGNAARDNKKTRIIPRHLQLAIRNDEELNKLLSGVTIAQGGVLPNIQAVLLPKKTEKKA
123
P84051
2
124
99.2%
UniRef90_P84051
2
124
secondary structure
helix
17
21
secondary structure
helix
27
36
secondary structure
beta
42
43
secondary structure
helix
46
72
secondary structure
beta
77
78
secondary structure
helix
80
88
secondary structure
helix
91
96
secondary structure
helix
113
115
pfam
PF00125.21
Histone
4
90
pfam
PF16211.2
Histone_H2A_C
91
124
D
Histone H2B
Drosophila melanogaster
IPPKTSGKAAKKAGKAQKNITKTDKKKKRKRKESYAIYIYTVLKQVHPDTGISSKAMSIMNSFVNDIFERIAAEASRLAHYNKRSTITSREIQTAVRLLLPGELAKHAVSEGTKAVTKYTSSK
123
P02283
1
123
100%
UniRef90_P02283
1
123
secondary structure
helix
36
46
secondary structure
beta
51
52
secondary structure
helix
54
81
secondary structure
beta
86
87
secondary structure
helix
89
99
secondary structure
helix
102
121
pfam
PF00125.21
Histone
2
99
Histones form parts of the nucleosome particle by dimerization and subsequent multimerization (PMID:1946434). The dimer contains both histone subunits in a highly intertwined conformation reflecting the possible domain-swapped origins of the structure (PMID:17391511). Accordingly, this dimerization has been experimentally characterized to be coupled to the structure formation of both interacting partners (PMID:12779337); this synergistic folding has been shown separately for H2A-H2B dimers (PMID:15588829) and H3-H4 dimers as well (PMID:15096635). Histones containing various types of monomeric subunits can exhibit varying stability and folding kinetics. E.g. in the case of H3-H4 histones, the dimerization is a complex process with the two monomers first adopting an intermediate state upon encounter and then reaching the classical histone fold through restructurization (PMID:12779337). However, independent of composition and folding kinetics, all histones appear to fold in a cooperative fashion that is coupled to binding (PMID:11669650).
2pyo
4qlc
4x23
MF2200004
H2A-H2B histone dimer (human), containing histone variants H2A.V and H2B type 1-J
3waa
X-ray
3.20
heterodimer
Homo sapiens
24311584
Horikoshi N, Sato K, Shimada K, Arimura Y, Osakabe A, Tachiwana H, Hayashi-Takanaka Y, Iwasaki W, Kagawa W, Harata M, Kimura H, Kurumizaka H
Structural polymorphism in the L1 loop regions of human H2A.Z.1 and H2A.Z.2.
Acta Crystallogr. D Biol. Crystallogr.
2013
Pt 12
69
2431-9
The histone H2A.Z variant is widely conserved among eukaryotes. Two isoforms, H2A.Z.1 and H2A.Z.2, have been identified in vertebrates and may have distinct functions in cell growth and gene expression. However, no structural differences between H2A.Z.1 and H2A.Z.2 have been reported. In the present study, the crystal structures of nucleosomes containing human H2A.Z.1 and H2A.Z.2 were determined. The structures of the L1 loop regions were found to clearly differ between H2A.Z.1 and H2A.Z.2, although their amino-acid sequences in this region are identical. This structural polymorphism may have been induced by a substitution that evolutionally occurred at the position of amino acid 38 and by the flexible nature of the L1 loops of H2A.Z.1 and H2A.Z.2. It was also found that in living cells nucleosomal H2A.Z.1 exchanges more rapidly than H2A.Z.2. A mutational analysis revealed that the amino-acid difference at position 38 is at least partially responsible for the distinctive dynamics of H2A.Z.1 and H2A.Z.2. These findings provide important new information for understanding the differences in the regulation and functions of H2A.Z.1 and H2A.Z.2 in cells.
GO:0003677
DNA binding
GO:0046982
protein heterodimerization activity
GO:0005634
nucleus
GO:0000786
nucleosome
Chains A, B, E, F, G, H, I and J have been removed to highlight the basic interaction that forms the histone dimer composed of chains C and D.
2
2
Histone-like interactions
Histones
C
Histone H2A.V
Homo sapiens
GSHMAGGKAGKDSGKAKAKAVSRSQRAGLQFPVGRIHRHLKTRTTSHGRVGATAAVYSAAILEYLTAEVLELAGNASKDLKVKRITPRHLQLAIRGDEELDSLIKATIAGGGVIPHIHKSLIGKKGQQKTA
131
Q71UI9
1
128
100%
UniRef90_Q71UI9
1
128
secondary structure
helix
20
24
secondary structure
helix
30
38
secondary structure
beta
46
47
secondary structure
helix
49
75
secondary structure
beta
81
82
secondary structure
helix
84
93
secondary structure
helix
95
100
secondary structure
helix
116
118
pfam
PF00125.21
Histone
4
94
pfam
PF16211.2
Histone_H2A_C
95
128
D
Histone H2B type 1-J
Homo sapiens
GSHMPEPAKSAPAPKKGSKKAVTKAQKKDGKKRKRSRKESYSIYVYKVLKQVHPDTGISSKAMGIMNSFVNDIFERIAGEASRLAHYNKRSTITSREIQTAVRLLLPGELAKHAVSEGTKAVTKYTSAK
129
P06899
1
126
100%
UniRef90_P06899
1
126
secondary structure
helix
39
49
secondary structure
beta
54
55
secondary structure
helix
57
83
secondary structure
beta
89
90
secondary structure
helix
92
102
secondary structure
helix
105
124
pfam
PF00125.21
Histone
2
102
Histones form parts of the nucleosome particle by dimerization and subsequent multimerization (PMID:1946434). The dimer contains both histone subunits in a highly intertwined conformation reflecting the possible domain-swapped origins of the structure (PMID:17391511). Accordingly, this dimerization has been experimentally characterized to be coupled to the structure formation of both interacting partners (PMID:12779337); this synergistic folding has been shown separately for H2A-H2B dimers (PMID:15588829) and H3-H4 dimers as well (PMID:15096635). Histones containing various types of monomeric subunits can exhibit varying stability and folding kinetics. E.g. in the case of H3-H4 histones, the dimerization is a complex process with the two monomers first adopting an intermediate state upon encounter and then reaching the classical histone fold through restructurization (PMID:12779337). However, independent of composition and folding kinetics, all histones appear to fold in a cooperative fashion that is coupled to binding (PMID:11669650).
MF2200005
H3-H4 histone dimer (human), containing histone variant H3.1
3afa
X-ray
2.50
heterodimer
Homo sapiens
20498094
Tachiwana H, Kagawa W, Osakabe A, Kawaguchi K, Shiga T, Hayashi-Takanaka Y, Kimura H, Kurumizaka H
Structural basis of instability of the nucleosome containing a testis-specific histone variant, human H3T.
Proc. Natl. Acad. Sci. U.S.A.
2010
23
107
10454-9
A histone H3 variant, H3T, is highly expressed in the testis, suggesting that it may play an important role in the chromatin reorganization required for meiosis and/or spermatogenesis. In the present study, we found that the nucleosome containing human H3T is significantly unstable both in vitro and in vivo, as compared to the conventional nucleosome containing H3.1. The crystal structure of the H3T nucleosome revealed structural differences in the H3T regions on both ends of the central alpha2 helix, as compared to those of H3.1. The H3T-specific residues (Met71 and Val111) are the source of the structural differences observed between H3T and H3.1. A mutational analysis revealed that these residues are responsible for the reduced stability of the H3T-containing nucleosome. These physical and structural properties of the H3T-containing nucleosome may provide the basis of chromatin reorganization during spermatogenesis.
GO:0042393
histone binding
GO:0046982
protein heterodimerization activity
GO:0003677
DNA binding
GO:0000183
chromatin silencing at rDNA
GO:0031047
gene silencing by RNA
GO:0044267
cellular protein metabolic process
GO:0032200
telomere organization
GO:0051290
protein heterotetramerization
GO:0045815
positive regulation of gene expression, epigenetic
GO:0006335
DNA replication-dependent nucleosome assembly
GO:0000784
nuclear chromosome, telomeric region
GO:0016020
membrane
GO:0005654
nucleoplasm
GO:0070062
extracellular exosome
GO:0000786
nucleosome
Chains C, D, E, F, G, H, I and J have been removed to highlight the basic interaction that forms the histone dimer composed of chains A and B.
2
2
Histone-like interactions
Histones
A
Histone H3.1
Homo sapiens
GSHMARTKQTARKSTGGKAPRKQLATKAARKSAPATGGVKKPHRYRPGTVALREIRRYQKSTELLIRKLPFQRLVREIAQDFKTDLRFQSSAVMALQEACEAYLVGLFEDTNLCAIHAKRVTIMPKDIQLARRIRGERA
139
P68431
1
136
100%
UniRef90_P68431
1
136
secondary structure
helix
46
57
secondary structure
helix
65
77
secondary structure
beta
84
85
secondary structure
helix
87
114
secondary structure
beta
119
120
secondary structure
helix
122
132
pfam
PF00125.21
Histone
1
132
B
Histone H4
Homo sapiens
GSHMSGRGKGGKGLGKGGAKRHRKVLRDNIQGITKPAIRRLARRGGVKRISGLIYEETRGVLKVFLENVIRDAVTYTEHAKRKTVTAMDVVYALKRQGRTLYGFGG
106
P62805
1
103
100%
UniRef90_P62805
1
103
secondary structure
helix
27
29
secondary structure
helix
32
41
secondary structure
beta
46
47
secondary structure
helix
51
76
secondary structure
beta
81
82
secondary structure
helix
84
93
pfam
PF15511.3
CENP-T_C
18
99
Histones form parts of the nucleosome particle by dimerization and subsequent multimerization (PMID:1946434). The dimer contains both histone subunits in a highly intertwined conformation reflecting the possible domain-swapped origins of the structure (PMID:17391511). Accordingly, this dimerization has been experimentally characterized to be coupled to the structure formation of both interacting partners (PMID:12779337); this synergistic folding has been shown separately for H2A-H2B dimers (PMID:15588829) and H3-H4 dimers as well (PMID:15096635). Histones containing various types of monomeric subunits can exhibit varying stability and folding kinetics. E.g. in the case of H3-H4 histones, the dimerization is a complex process with the two monomers first adopting an intermediate state upon encounter and then reaching the classical histone fold through restructurization (PMID:12779337). However, independent of composition and folding kinetics, all histones appear to fold in a cooperative fashion that is coupled to binding (PMID:11669650).
3ayw
3aze
3azf
3azg
3azh
3azi
3azj
3azk
3azl
3azm
3azn
5c3i
2cv5
1u35
3w96
3w97
3w98
3w99
3wa9
3waa
3wkj
3x1s
3x1t
3x1u
3x1v
4ym5
4ym6
4z2m
5av5
5av6
5av8
5av9
5avb
5avc
5b24
5b2i
5b2j
5cpi
5cpj
5cpk
5gse
5gsu
5jrg
5b1l
5b1m
MF2200006
H3-H4 histone dimer (human), containing histone variant H3.2
3av1
X-ray
2.50
heterodimer
Homo sapiens
21636898
Tachiwana H, Osakabe A, Shiga T, Miya Y, Kimura H, Kagawa W, Kurumizaka H
Structures of human nucleosomes containing major histone H3 variants.
Acta Crystallogr. D Biol. Crystallogr.
2011
Pt 6
67
578-83
The nucleosome is the fundamental repeating unit of chromatin, via which genomic DNA is packaged into the nucleus in eukaryotes. In the nucleosome, two copies of each core histone, H2A, H2B, H3 and H4, form a histone octamer which wraps 146 base pairs of DNA around itself. All of the core histones except for histone H4 have nonallelic isoforms called histone variants. In humans, eight histone H3 variants, H3.1, H3.2, H3.3, H3T, H3.5, H3.X, H3.Y and CENP-A, have been reported to date. Previous studies have suggested that histone H3 variants possess distinct functions in the formation of specific chromosome regions and/or in the regulation of transcription and replication. H3.1, H3.2 and H3.3 are the most abundant H3 variants. Here, crystal structures of human nucleosomes containing either H3.2 or H3.3 have been solved. The structures were essentially the same as that of the H3.1 nucleosome. Since the amino-acid residues specific for H3.2 and H3.3 are located on the accessible surface of the H3/H4 tetramer, they may be potential interaction sites for H3.2- and H3.3-specific chaperones.
GO:0046982
protein heterodimerization activity
GO:0003677
DNA binding
GO:0042393
histone binding
GO:0045815
positive regulation of gene expression, epigenetic
GO:0006334
nucleosome assembly
GO:0000183
chromatin silencing at rDNA
GO:0031047
gene silencing by RNA
GO:0044267
cellular protein metabolic process
GO:0000786
nucleosome
GO:0070062
extracellular exosome
GO:0005654
nucleoplasm
Chains C, D, E, F, G and H have been removed to highlight the basic interaction that forms the histone dimer composed of chains A and B.
2
2
Histone-like interactions
Histones
A
Histone H3.2
Homo sapiens
GSHMARTKQTARKSTGGKAPRKQLATKAARKSAPATGGVKKPHRYRPGTVALREIRRYQKSTELLIRKLPFQRLVREIAQDFKTDLRFQSSAVMALQEASEAYLVGLFEDTNLCAIHAKRVTIMPKDIQLARRIRGERA
139
Q71DI3
1
136
100%
UniRef90_Q71DI3
1
136
secondary structure
helix
46
57
secondary structure
helix
65
77
secondary structure
beta
84
85
secondary structure
helix
87
114
secondary structure
beta
119
120
secondary structure
helix
122
132
pfam
PF00125.21
Histone
1
132
B
Histone H4
Homo sapiens
GSHMSGRGKGGKGLGKGGAKRHRKVLRDNIQGITKPAIRRLARRGGVKRISGLIYEETRGVLKVFLENVIRDAVTYTEHAKRKTVTAMDVVYALKRQGRTLYGFGG
106
P62805
1
103
100%
UniRef90_P62805
1
103
secondary structure
helix
27
29
secondary structure
helix
32
41
secondary structure
beta
46
47
secondary structure
helix
51
76
secondary structure
beta
81
82
secondary structure
helix
84
93
pfam
PF15511.3
CENP-T_C
18
99
Histones form parts of the nucleosome particle by dimerization and subsequent multimerization (PMID:1946434). The dimer contains both histone subunits in a highly intertwined conformation reflecting the possible domain-swapped origins of the structure (PMID:17391511). Accordingly, this dimerization has been experimentally characterized to be coupled to the structure formation of both interacting partners (PMID:12779337); this synergistic folding has been shown separately for H2A-H2B dimers (PMID:15588829) and H3-H4 dimers as well (PMID:15096635). Histones containing various types of monomeric subunits can exhibit varying stability and folding kinetics. E.g. in the case of H3-H4 histones, the dimerization is a complex process with the two monomers first adopting an intermediate state upon encounter and then reaching the classical histone fold through restructurization (PMID:12779337). However, independent of composition and folding kinetics, all histones appear to fold in a cooperative fashion that is coupled to binding (PMID:11669650).
2aro
5bo0
4eo5
1hio
3b6f
3b6g
5bs7
5bsa
1eqz
1f66
2f8n
2fj7
2hio
1hq3
2io5
4j8u
4j8v
4j8w
4j8x
4kgc
3kuy
3kwq
1kx3
1kx4
1kx5
3kxb
3lel
3lja
3lz0
3lz1
3mgp
3mgq
3mgr
3mgs
3mnn
2nzd
3o62
1p34
1p3a
1p3b
1p3f
1p3g
1p3i
1p3k
1p3l
1p3m
1p3o
1p3p
3reh
3rei
3rej
3rek
3rel
1s32
1tzy
3ut9
3uta
3utb
4wu8
4wu9
4xzq
4ys3
4z66
5b0y
5b0z
5b40
3c9k
2hue
3mvd
4r8p
5kgf
5mlu
MF2200007
H3-H4 histone dimer (human), containing histone variant H3.1t
3a6n
X-ray
2.70
heterodimer
Homo sapiens
20498094
Tachiwana H, Kagawa W, Osakabe A, Kawaguchi K, Shiga T, Hayashi-Takanaka Y, Kimura H, Kurumizaka H
Structural basis of instability of the nucleosome containing a testis-specific histone variant, human H3T.
Proc. Natl. Acad. Sci. U.S.A.
2010
23
107
10454-9
A histone H3 variant, H3T, is highly expressed in the testis, suggesting that it may play an important role in the chromatin reorganization required for meiosis and/or spermatogenesis. In the present study, we found that the nucleosome containing human H3T is significantly unstable both in vitro and in vivo, as compared to the conventional nucleosome containing H3.1. The crystal structure of the H3T nucleosome revealed structural differences in the H3T regions on both ends of the central alpha2 helix, as compared to those of H3.1. The H3T-specific residues (Met71 and Val111) are the source of the structural differences observed between H3T and H3.1. A mutational analysis revealed that these residues are responsible for the reduced stability of the H3T-containing nucleosome. These physical and structural properties of the H3T-containing nucleosome may provide the basis of chromatin reorganization during spermatogenesis.
GO:0042393
histone binding
GO:0046982
protein heterodimerization activity
GO:0003677
DNA binding
GO:0006303
double-strand break repair via nonhomologous end joining
GO:0051290
protein heterotetramerization
GO:0006334
nucleosome assembly
GO:0016233
telomere capping
GO:0005654
nucleoplasm
GO:0070062
extracellular exosome
GO:0000786
nucleosome
Chains C, D, E, F, G, H, I and J have been removed to highlight the basic interaction that forms the histone dimer composed of chains A and B.
2
2
Histone-like interactions
Histones
A
Histone H3.1t
Homo sapiens
GSHMARTKQTARKSTGGKAPRKQLATKVARKSAPATGGVKKPHRYRPGTVALREIRRYQKSTELLIRKLPFQRLMREIAQDFKTDLRFQSSAVMALQEACESYLVGLFEDTNLCVIHAKRVTIMPKDIQLARRIRGERA
139
Q16695
1
136
100%
UniRef90_Q16695
1
136
secondary structure
helix
46
57
secondary structure
helix
65
76
secondary structure
beta
84
85
secondary structure
helix
87
114
secondary structure
beta
119
120
secondary structure
helix
122
131
pfam
PF00125.21
Histone
1
132
B
Histone H4
Homo sapiens
GSHMSGRGKGGKGLGKGGAKRHRKVLRDNIQGITKPAIRRLARRGGVKRISGLIYEETRGVLKVFLENVIRDAVTYTEHAKRKTVTAMDVVYALKRQGRTLYGFGG
106
P62805
1
103
100%
UniRef90_P62805
1
103
secondary structure
helix
27
29
secondary structure
helix
32
41
secondary structure
beta
46
47
secondary structure
helix
51
76
secondary structure
beta
81
82
secondary structure
helix
84
93
pfam
PF15511.3
CENP-T_C
18
99
Histones form parts of the nucleosome particle by dimerization and subsequent multimerization (PMID:1946434). The dimer contains both histone subunits in a highly intertwined conformation reflecting the possible domain-swapped origins of the structure (PMID:17391511). Accordingly, this dimerization has been experimentally characterized to be coupled to the structure formation of both interacting partners (PMID:12779337); this synergistic folding has been shown separately for H2A-H2B dimers (PMID:15588829) and H3-H4 dimers as well (PMID:15096635). Histones containing various types of monomeric subunits can exhibit varying stability and folding kinetics. E.g. in the case of H3-H4 histones, the dimerization is a complex process with the two monomers first adopting an intermediate state upon encounter and then reaching the classical histone fold through restructurization (PMID:12779337). However, independent of composition and folding kinetics, all histones appear to fold in a cooperative fashion that is coupled to binding (PMID:11669650).
1aoi
3c1b
3c1c
1m18
1m19
1m1a
MF2200008
H3-H4 histone dimer (human), containing histone variant H3.3
3av2
X-ray
2.80
heterodimer
Homo sapiens
21636898
Tachiwana H, Osakabe A, Shiga T, Miya Y, Kimura H, Kagawa W, Kurumizaka H
Structures of human nucleosomes containing major histone H3 variants.
Acta Crystallogr. D Biol. Crystallogr.
2011
Pt 6
67
578-83
The nucleosome is the fundamental repeating unit of chromatin, via which genomic DNA is packaged into the nucleus in eukaryotes. In the nucleosome, two copies of each core histone, H2A, H2B, H3 and H4, form a histone octamer which wraps 146 base pairs of DNA around itself. All of the core histones except for histone H4 have nonallelic isoforms called histone variants. In humans, eight histone H3 variants, H3.1, H3.2, H3.3, H3T, H3.5, H3.X, H3.Y and CENP-A, have been reported to date. Previous studies have suggested that histone H3 variants possess distinct functions in the formation of specific chromosome regions and/or in the regulation of transcription and replication. H3.1, H3.2 and H3.3 are the most abundant H3 variants. Here, crystal structures of human nucleosomes containing either H3.2 or H3.3 have been solved. The structures were essentially the same as that of the H3.1 nucleosome. Since the amino-acid residues specific for H3.2 and H3.3 are located on the accessible surface of the H3/H4 tetramer, they may be potential interaction sites for H3.2- and H3.3-specific chaperones.
GO:0042393
histone binding
GO:0003677
DNA binding
GO:0046982
protein heterodimerization activity
GO:0000183
chromatin silencing at rDNA
GO:0044267
cellular protein metabolic process
GO:0031047
gene silencing by RNA
GO:0032200
telomere organization
GO:0006336
DNA replication-independent nucleosome assembly
GO:0045815
positive regulation of gene expression, epigenetic
GO:0005654
nucleoplasm
GO:0000784
nuclear chromosome, telomeric region
GO:0070062
extracellular exosome
GO:0000786
nucleosome
Chains C, D, E, F, G, H, I and J have been removed to highlight the basic interaction that forms the histone dimer composed of chains A and B.
2
2
Histone-like interactions
Histones
A
Histone H3.3
Homo sapiens
GSHMARTKQTARKSTGGKAPRKQLATKAARKSAPSTGGVKKPHRYRPGTVALREIRRYQKSTELLIRKLPFQRLVREIAQDFKTDLRFQSAAIGALQEASEAYLVGLFEDTNLCAIHAKRVTIMPKDIQLARRIRGERA
139
P84243
1
136
100%
UniRef90_P84243
1
136
secondary structure
helix
46
55
secondary structure
helix
65
77
secondary structure
beta
84
85
secondary structure
helix
87
114
secondary structure
beta
119
120
secondary structure
helix
122
131
pfam
PF00125.21
Histone
1
132
B
Histone H4
Homo sapiens
GSHMSGRGKGGKGLGKGGAKRHRKVLRDNIQGITKPAIRRLARRGGVKRISGLIYEETRGVLKVFLENVIRDAVTYTEHAKRKTVTAMDVVYALKRQGRTLYGFGG
106
P62805
1
103
100%
UniRef90_P62805
1
103
secondary structure
helix
27
29
secondary structure
helix
32
41
secondary structure
beta
46
47
secondary structure
helix
51
76
secondary structure
beta
81
82
secondary structure
helix
84
93
pfam
PF15511.3
CENP-T_C
18
99
Histones form parts of the nucleosome particle by dimerization and subsequent multimerization (PMID:1946434). The dimer contains both histone subunits in a highly intertwined conformation reflecting the possible domain-swapped origins of the structure (PMID:17391511). Accordingly, this dimerization has been experimentally characterized to be coupled to the structure formation of both interacting partners (PMID:12779337); this synergistic folding has been shown separately for H2A-H2B dimers (PMID:15588829) and H3-H4 dimers as well (PMID:15096635). Histones containing various types of monomeric subunits can exhibit varying stability and folding kinetics. E.g. in the case of H3-H4 histones, the dimerization is a complex process with the two monomers first adopting an intermediate state upon encounter and then reaching the classical histone fold through restructurization (PMID:12779337). However, independent of composition and folding kinetics, all histones appear to fold in a cooperative fashion that is coupled to binding (PMID:11669650).
4h9n
4h9o
4h9r
4h9s
4hga
3wtp
5b32
5b33
4h9p
4h9q
5ay8
5bnv
5bnx
5ja4
5kdm
5x7x
4zbj
MF2210004
H3-H4 histone dimer (Drosophila melanogaster)
2nqb
X-ray
2.30
heterodimer
Drosophila melanogaster
Chakravarthy, S., Luger, K.
Comparative analysis of nucleosome structures from different species.
To be published
-
GO:0046982
protein heterodimerization activity
GO:0003677
DNA binding
GO:0006334
nucleosome assembly
GO:0035059
RCAF complex
GO:0000786
nucleosome
Chains C, D, E, F, G, H, I and J have been removed to highlight the basic interaction that forms the histone dimer composed of chains A and B.
2
2
Histone-like interactions
Histones
A
Histone H3
Drosophila melanogaster
ARTKQTARKSTGGKAPRKQLATKAARKSAPATGGVKKPHRYRPGTVALREIRRYQKSTELLIRKLPFQRLVREIAQDFKTDLRFQSSAVMALQEASEAYLVGLFEDTNLCAIHAKRVTIMPKDIQLARRIRGERA
135
P02299
2
136
99.3%
UniRef90_Q71DI3
2
136
secondary structure
helix
46
57
secondary structure
helix
65
77
secondary structure
beta
84
85
secondary structure
helix
87
114
secondary structure
beta
119
120
secondary structure
helix
122
132
pfam
PF00125.21
Histone
1
132
B
Histone H4
Drosophila melanogaster
ITGRGKGGKGLGKGGAKRHRKVLRDNIQGITKPAIRRLARRGGVKRISGLIYEETRGVLKVFLENVIRDAVTYTEHAKRKTVTAMDVVYALKRQGRTLYGFGG
103
P84040
1
103
100%
UniRef90_P84040
1
103
secondary structure
helix
26
29
secondary structure
helix
32
41
secondary structure
beta
46
47
secondary structure
helix
51
76
secondary structure
beta
81
82
secondary structure
helix
84
93
pfam
PF15511.3
CENP-T_C
18
99
Histones form parts of the nucleosome particle by dimerization and subsequent multimerization (PMID:1946434). The dimer contains both histone subunits in a highly intertwined conformation reflecting the possible domain-swapped origins of the structure (PMID:17391511). Accordingly, this dimerization has been experimentally characterized to be coupled to the structure formation of both interacting partners (PMID:12779337); this synergistic folding has been shown separately for H2A-H2B dimers (PMID:15588829) and H3-H4 dimers as well (PMID:15096635). Histones containing various types of monomeric subunits can exhibit varying stability and folding kinetics. E.g. in the case of H3-H4 histones, the dimerization is a complex process with the two monomers first adopting an intermediate state upon encounter and then reaching the classical histone fold through restructurization (PMID:12779337). However, independent of composition and folding kinetics, all histones appear to fold in a cooperative fashion that is coupled to binding (PMID:11669650).
2pyo
4uuz
4qlc
4x23
MF2210005
H3-H4 histone dimer (Saccharomyces cerevisiae)
1id3
X-ray
3.10
heterodimer
Saccharomyces cerevisiae
11566884
White CL, Suto RK, Luger K
Structure of the yeast nucleosome core particle reveals fundamental changes in internucleosome interactions.
EMBO J.
2001
18
20
5207-18
Chromatin is composed of nucleosomes, the universally repeating protein-DNA complex in eukaryotic cells. The crystal structure of the nucleosome core particle from Saccharomyces cerevisiae reveals that the structure and function of this fundamental complex is conserved between single-cell organisms and metazoans. Our results show that yeast nucleosomes are likely to be subtly destabilized as compared with nucleosomes from higher eukaryotes, consistent with the idea that much of the yeast genome remains constitutively open during much of its life cycle. Importantly, minor sequence variations lead to dramatic changes in the way in which nucleosomes pack against each other within the crystal lattice. This has important implications for our understanding of the formation of higher order chromatin structure and its modulation by post-translational modifications. Finally, the yeast nucleosome core particle provides a structural context by which to interpret genetic data obtained from yeast. Coordinates have been deposited with the Protein Data Bank under accession number 1ID3.
GO:0046982
protein heterodimerization activity
GO:0003677
DNA binding
GO:0043935
sexual sporulation resulting in formation of a cellular spore
GO:0006333
chromatin assembly or disassembly
GO:0000788
nuclear nucleosome
GO:0031298
replication fork protection complex
Chains C, D, E, F, G, H, I and J have been removed to highlight the basic interaction that forms the histone dimer composed of chains A and B.
2
2
Histone-like interactions
Histones
A
Histone H3
Saccharomyces cerevisiae
ARTKQTARKSTGGKAPRKQLASKAARKSAPSTGGVKKPHRYKPGTVALREIRRFQKSTELLIRKLPFQRLVREIAQDFKTDLRFQSSAIGALQESVEAYLVSLFEDTNLAAIHAKRVTIQKKEIKLARRLRGERS
135
P61830
2
136
99.3%
UniRef90_Q757N1
2
136
secondary structure
helix
46
57
secondary structure
helix
65
77
secondary structure
beta
84
85
secondary structure
helix
87
114
secondary structure
beta
119
120
secondary structure
helix
122
130
pfam
PF00125.21
Histone
1
132
B
Histone H4
Saccharomyces cerevisiae
SGRGKGGKGLGKGGAKRHRKILRDNIQGITKPAIRRLARRGGVKRISGLIYEEVRAVLKSFLESVIRDSVTYTEHAKRKTVTSLDVVYALKRQGRTLYGFGG
102
P02309
2
103
99%
UniRef90_P02309
2
103
secondary structure
helix
27
29
secondary structure
helix
32
41
secondary structure
beta
46
47
secondary structure
helix
51
76
secondary structure
beta
81
82
secondary structure
helix
84
93
pfam
PF15511.3
CENP-T_C
19
99
Histones form parts of the nucleosome particle by dimerization and subsequent multimerization (PMID:1946434). The dimer contains both histone subunits in a highly intertwined conformation reflecting the possible domain-swapped origins of the structure (PMID:17391511). Accordingly, this dimerization has been experimentally characterized to be coupled to the structure formation of both interacting partners (PMID:12779337); this synergistic folding has been shown separately for H2A-H2B dimers (PMID:15588829) and H3-H4 dimers as well (PMID:15096635). Histones containing various types of monomeric subunits can exhibit varying stability and folding kinetics. E.g. in the case of H3-H4 histones, the dimerization is a complex process with the two monomers first adopting an intermediate state upon encounter and then reaching the classical histone fold through restructurization (PMID:12779337). However, independent of composition and folding kinetics, all histones appear to fold in a cooperative fashion that is coupled to binding (PMID:11669650).
4jjn
4kud
MF4110005
Transthyretin (Gallus gallus)
1tfp
X-ray
2.90
homotetramer (dimer of dimers)
Gallus gallus
8612621
Sunde M, Richardson SJ, Chang L, Pettersson TM, Schreiber G, Blake CC
The crystal structure of transthyretin from chicken.
Eur. J. Biochem.
1996
2
236
491-9
The crystal structure of chicken transthyretin has been solved at 290-pm resolution by molecular-replacement techniques. Transthyretin is the protein component of the amyloid fibrils found in patients suffering from either familial amyloidotic polyneuropathy or senile systemic amyloidosis. Familial amyloidotic polyneuropathy is an autosomal dominant hereditary type of amyloidosis which involves transthyretin with either one or two amino acid substitutions. The three-dimensional structure of chicken transthyretin was determined in order to compare a non-amyloidogenic, species-variant transthyretin with wild-type and mutant transthyretin molecules. Of the 31 chicken-to-human residue differences, 9 occur at positions which in human transthyretin give rise to amyloidogenic variants although none corresponds to the appropriate side-chain substitutions. The model of chicken transthyretin has been refined to an R-factor of 19.9%. The overall fold of the protein is that of an all-beta protein. Compared with wild-type human transthyretin the avian transthyretin shows quite large differences in the region known to be involved in binding to retinol-binding protein, it has a much shorter helical component than the human protein and some of the monomer-monomer interactions are different.
GO:0036094
small molecule binding
GO:0005179
hormone activity
GO:0046982
protein heterodimerization activity
GO:0070324
thyroid hormone binding
GO:0042802
identical protein binding
GO:0019904
protein domain specific binding
GO:0001555
oocyte growth
GO:0042572
retinol metabolic process
GO:0051262
protein tetramerization
GO:0070327
thyroid hormone transport
GO:0009615
response to virus
GO:0005615
extracellular space
GO:0070062
extracellular exosome
GO:0043234
protein complex
GO:0030136
clathrin-coated vesicle
GO:0060417
yolk
Chains C and D were generated from chains A and B respectively, using the biomatrices described in the original PDB file.
4
1
Transthyretin-like folds
Transthyretin
A
Transthyretin
Gallus gallus
APLVSHGSVDSKCPLMVKVLDAVRGSPAANVAVKVFKKAADGTWQDFATGKTTEFGEIHELTTEEQFVEGVYRVEFDTSSYWKGLGLSPFHEYADVVFTANDSGHRHYTIAALLSPFSYSTTAVVSDPQE
130
P27731
21
150
86.7%
UniRef90_P27731
21
150
secondary structure
beta
35
41
secondary structure
beta
46
47
secondary structure
beta
52
58
secondary structure
beta
64
71
secondary structure
beta
90
97
secondary structure
helix
103
105
secondary structure
beta
113
120
secondary structure
beta
128
134
secondary structure
beta
138
145
pfam
PF00576.18
Transthyretin
35
142
B
Transthyretin
Gallus gallus
APLVSHGSVDSKCPLMVKVLDAVRGSPAANVAVKVFKKAADGTWQDFATGKTTEFGEIHELTTEEQFVEGVYRVEFDTSSYWKGLGLSPFHEYADVVFTANDSGHRHYTIAALLSPFSYSTTAVVSDPQE
130
P27731
21
150
86.7%
UniRef90_P27731
21
150
secondary structure
beta
35
41
secondary structure
beta
46
47
secondary structure
beta
52
58
secondary structure
beta
64
71
secondary structure
beta
90
97
secondary structure
beta
112
120
secondary structure
beta
128
134
secondary structure
beta
138
145
pfam
PF00576.18
Transthyretin
35
142
C
Transthyretin
Gallus gallus
APLVSHGSVDSKCPLMVKVLDAVRGSPAANVAVKVFKKAADGTWQDFATGKTTEFGEIHELTTEEQFVEGVYRVEFDTSSYWKGLGLSPFHEYADVVFTANDSGHRHYTIAALLSPFSYSTTAVVSDPQE
130
P27731
21
150
86.7%
UniRef90_P27731
21
150
secondary structure
beta
35
41
secondary structure
beta
46
47
secondary structure
beta
52
58
secondary structure
beta
64
71
secondary structure
beta
90
97
secondary structure
helix
103
105
secondary structure
beta
113
120
secondary structure
beta
128
134
secondary structure
beta
138
145
pfam
PF00576.18
Transthyretin
35
142
D
Transthyretin
Gallus gallus
APLVSHGSVDSKCPLMVKVLDAVRGSPAANVAVKVFKKAADGTWQDFATGKTTEFGEIHELTTEEQFVEGVYRVEFDTSSYWKGLGLSPFHEYADVVFTANDSGHRHYTIAALLSPFSYSTTAVVSDPQE
130
P27731
21
150
86.7%
UniRef90_P27731
21
150
secondary structure
beta
35
41
secondary structure
beta
46
47
secondary structure
beta
52
58
secondary structure
beta
64
71
secondary structure
beta
90
97
secondary structure
beta
112
120
secondary structure
beta
128
134
secondary structure
beta
138
145
pfam
PF00576.18
Transthyretin
35
142
Transthyretin was shown in calorimetrics experiments to follow two-state folding/binding kinetics with the emergence of structure being linked to oligomerization (PMID:11152276).
MF2202002
GTPase binding domain of Wiskott-Aldrich syndrome protein in complex with E. coli EspF(U)
2k42
NMR
heterodimer
Homo sapiens / Escherichia coli O157:H7
18650809
Cheng HC, Skehan BM, Campellone KG, Leong JM, Rosen MK
Structural mechanism of WASP activation by the enterohaemorrhagic E. coli effector EspF(U).
Nature
2008
7207
454
1009-13
During infection, enterohaemorrhagic Escherichia coli (EHEC) takes over the actin cytoskeleton of eukaryotic cells by injecting the EspF(U) protein into the host cytoplasm. EspF(U) controls actin by activating members of the Wiskott-Aldrich syndrome protein (WASP) family. Here we show that EspF(U) binds to the autoinhibitory GTPase binding domain (GBD) in WASP proteins and displaces it from the activity-bearing VCA domain (for verprolin homology, central hydrophobic and acidic regions). This interaction potently activates WASP and neural (N)-WASP in vitro and induces localized actin assembly in cells. In the solution structure of the GBD-EspF(U) complex, EspF(U) forms an amphipathic helix that binds the GBD, mimicking interactions of the VCA domain in autoinhibited WASP. Thus, EspF(U) activates WASP by competing directly for the VCA binding site on the GBD. This mechanism is distinct from that used by the eukaryotic activators Cdc42 and SH2 domains, which globally destabilize the GBD fold to release the VCA. Such diversity of mechanism in WASP proteins is distinct from other multimodular systems, and may result from the intrinsically unstructured nature of the isolated GBD and VCA elements. The structural incompatibility of the GBD complexes with EspF(U) and Cdc42/SH2, plus high-affinity EspF(U) binding, enable EHEC to hijack the eukaryotic cytoskeletal machinery effectively.
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
2
Other
Other
A
Wiskott-Aldrich syndrome protein
Homo sapiens
GHMSGFKHVSHVGWDPQNGFDVNNLDPDLRSLFSRAGISEAQLTDAETSKLIYDFIEDQGGLEAVRQEMRRQ
72
P42768
239
310
14.3%
UniRef90_P42768
239
310
secondary structure
beta
252
253
secondary structure
beta
257
258
secondary structure
helix
265
274
secondary structure
helix
278
281
secondary structure
helix
284
296
secondary structure
helix
300
307
pfam
PF00786.25
PBD
237
296
B
Secreted effector protein EspF(U)
Escherichia coli O157:H7
GHMLPDVAQRLMQHLAEHGIQPARNMAEHIPPAPNW
36
P0DJ89
218
253
10.7%
UniRef90_P0DJ88
221
253
secondary structure
helix
224
233
pfam
PF04806.9
EspF
190
236
pfam
PF04806.9
EspF
237
283
A
The 230-249 region described in DisProt entry DP00215 and the 230-310 region described in IDEAL entry IID00269 cover 100% of the sequence present in the structure.
B
The 221-314 region described in IDEAL entry IID90008 covers 92% of the sequence present in the structure.
MF2110009
HY5 leucine zipper homodimer
2oqq
X-ray
2.00
homodimer
Arabidopsis thaliana
Yoon, M.-K., Kim, H.M., Choi, G., Lee, J.-O., Choi, B.-S.
Structural basis for the conformational integrity of the Arabidopsis thaliana HY5 Ieucine zipper homodimer
To be published
-
GO:0043565
sequence-specific DNA binding
GO:0003690
double-stranded DNA binding
GO:0003700
transcription factor activity, sequence-specific DNA binding
GO:0005515
protein binding
GO:0010218
response to far red light
GO:0009737
response to abscisic acid
GO:0031539
positive regulation of anthocyanin metabolic process
GO:0010114
response to red light
GO:0006355
regulation of transcription, DNA-templated
GO:0009740
gibberellic acid mediated signaling pathway
GO:0010099
regulation of photomorphogenesis
GO:0010224
response to UV-B
GO:0080167
response to karrikin
GO:0009585
red, far-red light phototransduction
GO:0042753
positive regulation of circadian rhythm
GO:0006351
transcription, DNA-templated
GO:0005634
nucleus
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Coils and zippers
Leucine zipper (dimeric)
A
Transcription factor HY5
Arabidopsis thaliana
GSAYLSELENRVKDLENKNSELEERLSTLQNENQMLRHILKN
42
O24646
109
150
25%
UniRef90_O24646
111
150
secondary structure
helix
111
149
pfam
PF00170.18
bZIP_1
86
150
B
Transcription factor HY5
Arabidopsis thaliana
GSAYLSELENRVKDLENKNSELEERLSTLQNENQMLRHILKN
42
O24646
109
150
25%
UniRef90_O24646
111
150
secondary structure
helix
111
149
pfam
PF00170.18
bZIP_1
86
150
The subunits in the structure are bound via coiled coil interactions. Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure. Leucine zippers, phenylalanine zippers and alanine zippers are subclasses of coiled coils where the hydrophobic interactions between subunits are predominantly formed by leucine, phenylalanine or alanine residues, respectively.
MF2211002
c-Myc-Max heterodimeric leucine zipper
1a93
NMR
heterodimer
Pan paniscus / Mus musculus
9680483
Lavigne P, Crump MP, Gagné SM, Hodges RS, Kay CM, Sykes BD
Insights into the mechanism of heterodimerization from the 1H-NMR solution structure of the c-Myc-Max heterodimeric leucine zipper.
J. Mol. Biol.
1998
1
281
165-81
The oncoprotein c-Myc (a member of the helix-loop-helix-leucine zipper (b-HLH-LZ) family of transcription factors) must heterodimerize with the b-HLH-LZ Max protein to bind DNA and activate transcription. It has been shown that the LZ domains of the c-Myc and Max proteins specifically form a heterodimeric LZ at 20 degreesC and neutral pH. This suggests that the LZ domains of the c-Myc and Max proteins are playing an important role in the heterodimerization of the corresponding gene products in vivo. Initially, to gain an insight into the energetics of heterodimerization, we studied the stability of N-terminal disulfide-linked versions of the c-Myc and Max homodimeric LZs and c-Myc-Max heterodimeric LZ by fitting the temperature-induced denaturation curves monitored by circular dichroism spectroscopy. The c-Myc LZ does not homodimerize (as previously reported) and the c-Myc-Max heterodimeric LZ is more stable than the Max homodimeric LZ at 20 degreesC and pH 7.0. In order to determine the critical interhelical interactions responsible for the molecular recognition between the c-Myc and Max LZs, the solution structure of the disulfide-linked c-Myc-Max heterodimeric LZ was solved by two-dimensional 1H-NMR techniques at 25 degreesC and pH 4.7. Both LZs are alpha-helical and the tertiary structure depicts the typical left-handed super-helical twist of a two-stranded parallel alpha-helical coiled-coil. A buried salt bridge involving a histidine on the Max LZ and two glutamate residues on the c-Myc LZ is observed at the interface of the heterodimeric LZ. A buried H-bond between an asparagine side-chain and a backbone carbonyl is also observed. Moreover, evidence for e-g interhelical salt bridges is reported. These specific interactions give insights into the preferential heterodimerization process of the two LZs. The low stabilities of the Max homodimeric LZ and the c-Myc-Max heterodimeric LZ as well as the specific interactions observed are discussed with regard to regulation of transcription in this family of transcription factors.
GO:0046983
protein dimerization activity
GO:0003677
DNA binding
GO:0006351
transcription, DNA-templated
GO:0006355
regulation of transcription, DNA-templated
GO:0005654
nucleoplasm
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
2
Coils and zippers
Leucine zipper (dimeric)
A
Myc proto-oncogene protein
Pan paniscus
CGGVQAEEQKLISEEDLLRKRREQLKHKLEQL
32
A1YG22
406
434
6.6%
UniRef90_P01106
406
434
secondary structure
helix
406
433
pfam
PF02344.12
Myc-LZ
408
438
B
Protein max
Mus musculus
CGGMRRKNDTHQQDIDDLKRQNALLEQQVRAL
32
P28574
74
102
18.1%
UniRef90_P61244
74
102
secondary structure
helix
74
101
The subunits in the structure are bound via coiled coil interactions (PMID:9680483). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure. Leucine zippers, phenylalanine zippers and alanine zippers are subclasses of coiled coils where the hydrophobic interactions between subunits are predominantly formed by leucine, phenylalanine or alanine residues, respectively.
A
The 406-434 region described in DisProt entry DP00260 covers 100% of a close homologue of the sequence present in the structure.
B
The 1-110 region described in DisProt entry DP00084 covers 100% of a close homologue of the sequence present in the structure.
2a93
1nkp
MF2201008
Heterodimer of ATF-4 and C/EBP beta
1ci6
X-ray
2.60
heterodimer
Homo sapiens / Mus musculus
11018027
Podust LM, Krezel AM, Kim Y
Crystal structure of the CCAAT box/enhancer-binding protein beta activating transcription factor-4 basic leucine zipper heterodimer in the absence of DNA.
J. Biol. Chem.
2001
1
276
505-13
The crystal structure of the heterodimer formed by the basic leucine zipper (bZIP) domains of activating transcription factor-4 (ATF4) and CCAAT box/enhancer-binding protein beta (C/EBP beta), from two different bZIP transcription factor families, has been determined and refined to 2.6 A. The structure shows that the heterodimer forms an asymmetric coiled-coil. Even in the absence of DNA, the basic region of ATF4 forms a continuous alpha-helix, but the basic region of C/EBP beta is disordered. Proteolysis, electrophoretic mobility shift assay, circular dichroism, and NMR analyses indicated that (i) the bZIP domain of ATF4 is a disordered monomer and forms a homodimer upon binding to the DNA target; (ii) the bZIP domain of ATF4 forms a heterodimer with the bZIP domain of C/EBP beta that binds the cAMP response element, but not CCAAT box DNA, with high affinity; and (iii) the basic region of ATF4 has a higher alpha-helical propensity than that of C/EBP beta. These results suggest that the degree of ordering of the basic region and the fork and the dimerization properties of the leucine zipper combine to distinguish the structurally similar bZIP domains of ATF4 and C/EBP beta with respect to DNA target sequence. This study provides insight into the mechanism by which dimeric bZIP transcription factors discriminate between closely related but distinct DNA targets.
GO:0000978
RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0008134
transcription factor binding
GO:0046982
protein heterodimerization activity
GO:0001077
transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:1990440
positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress
GO:0070059
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
GO:0006366
transcription from RNA polymerase II promoter
GO:0005654
nucleoplasm
GO:0005737
cytoplasm
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
2
Coils and zippers
Leucine zipper (dimeric)
A
Cyclic AMP-dependent transcription factor ATF-4
Homo sapiens
MKKLKKMEQNKTAATRYRQKKRAEQEALTGECKELEKKNEALKERADSLAKEIQYLKDLIEEV
63
P18848
279
341
17.9%
UniRef90_P18848
280
341
secondary structure
helix
288
340
pfam
PF00170.18
bZIP_1
276
339
B
CCAAT/enhancer-binding protein beta
Mus musculus
MEYKMRRERNNIAVRKSRDKAKMRNLETQHKVLELTAENERLQKKVEQLSRELSTLRNLFKQL
63
P28033
223
285
21.3%
UniRef90_P28033
224
285
secondary structure
helix
240
282
pfam
PF07716.12
bZIP_2
221
274
The subunits of the dimer were shown to be disordered in their monomeric form with the structure arising as a result of the interaction (PMID:11018027). The subunits in the structure are bound via coiled coil interactions (PMID:11018027). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure. Leucine zippers, phenylalanine zippers and alanine zippers are subclasses of coiled coils where the hydrophobic interactions between subunits are predominantly formed by leucine, phenylalanine or alanine residues, respectively.
B
A homologue sharing the same Pfam domain (PF07716.12) has been experimentally characterized as disordered in DisProt entry DP00083.
MF4110006
General corepressor Tup1p
3vp8
X-ray
1.91
homotetramer
Saccharomyces cerevisiae
22707714
Matsumura H, Kusaka N, Nakamura T, Tanaka N, Sagegami K, Uegaki K, Inoue T, Mukai Y
Crystal structure of the N-terminal domain of the yeast general corepressor Tup1p and its functional implications.
J. Biol. Chem.
2012
32
287
26528-38
The yeast Cyc8p-Tup1p protein complex is a general transcriptional corepressor of genes involved in many different physiological processes. Herein, we present the crystal structure of the Tup1p N-terminal domain (residues 1-92), essential for Tup1p self-assembly and interaction with Cyc8p. This domain tetramerizes to form a novel antiparallel four-helix bundle. Coiled coil interactions near the helical ends hold each dimer together, whereas interdimeric association involves only two sets of two residues located toward the chain centers. A mutagenesis study confirmed that the nonpolar residues responsible for the association of the protomers as dimers are also required for transcriptional repression. An additional structural study demonstrated that the domain containing an Leu(62) → Arg mutation that had been shown not to bind Cyc8p exhibits an altered structure, distinct from the wild type. This altered structure explains why the mutant cannot bind Cyc8p. The data presented herein highlight the importance of the architecture of the Tup1p N-terminal domain for self-association.
GO:0036033
mediator complex binding
GO:0042393
histone binding
GO:0080025
phosphatidylinositol-3,5-bisphosphate binding
GO:0001191
transcriptional repressor activity, RNA polymerase II transcription factor binding
GO:0042826
histone deacetylase binding
GO:2001020
regulation of response to DNA damage stimulus
GO:0043486
histone exchange
GO:0000433
negative regulation of transcription from RNA polymerase II promoter by glucose
GO:0007070
negative regulation of transcription from RNA polymerase II promoter during mitosis
GO:2000531
regulation of fatty acid biosynthetic process by regulation of transcription from RNA polymerase II promoter
GO:0001198
negative regulation of mating-type specific transcription from RNA polymerase II promoter
GO:0006351
transcription, DNA-templated
GO:0016584
nucleosome positioning
GO:2000217
regulation of invasive growth in response to glucose limitation
GO:0035955
negative regulation of dipeptide transport by negative regulation of transcription from RNA polymerase II promoter
GO:0008023
transcription elongation factor complex
GO:0033588
Elongator holoenzyme complex
GO:0000123
histone acetyltransferase complex
GO:0017053
transcriptional repressor complex
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
1
Coils and zippers
Coiled coil (tetrameric)
A
General transcriptional corepressor TUP1
Saccharomyces cerevisiae
MTASVSNTQNKLNELLDAIRQEFLQVSQEANTYRLQNQKDYDFKMNQQLAEMQQIRNTVYELELTHRKMKDAYEEEIKHLKLGLEQRDHQIA
92
P16649
1
92
12.9%
UniRef90_P16649
1
92
secondary structure
helix
5
76
pfam
PF08581.7
Tup_N
11
88
B
General transcriptional corepressor TUP1
Saccharomyces cerevisiae
MTASVSNTQNKLNELLDAIRQEFLQVSQEANTYRLQNQKDYDFKMNQQLAEMQQIRNTVYELELTHRKMKDAYEEEIKHLKLGLEQRDHQIA
92
P16649
1
92
12.9%
UniRef90_P16649
1
92
secondary structure
helix
3
28
secondary structure
helix
30
80
pfam
PF08581.7
Tup_N
11
88
C
General transcriptional corepressor TUP1
Saccharomyces cerevisiae
MTASVSNTQNKLNELLDAIRQEFLQVSQEANTYRLQNQKDYDFKMNQQLAEMQQIRNTVYELELTHRKMKDAYEEEIKHLKLGLEQRDHQIA
92
P16649
1
92
12.9%
UniRef90_P16649
1
92
secondary structure
helix
6
79
pfam
PF08581.7
Tup_N
11
88
D
General transcriptional corepressor TUP1
Saccharomyces cerevisiae
MTASVSNTQNKLNELLDAIRQEFLQVSQEANTYRLQNQKDYDFKMNQQLAEMQQIRNTVYELELTHRKMKDAYEEEIKHLKLGLEQRDHQIA
92
P16649
1
92
12.9%
UniRef90_P16649
1
92
secondary structure
helix
4
77
pfam
PF08581.7
Tup_N
11
88
The subunits in the structure are bound via coiled coil interactions (PMID:22707714). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
3vp9
MF2120017
TrpR-like protein (Eubacterium eligens)
3g1c
X-ray
2.20
homodimer
Eubacterium eligens
Zhang, R., Hendricks, R., Freeman, L., Babnigg, G., Joachimiak, A.
The crystal structure of a TrpR like protein from Eubacterium eligens ATCC 27750
To be published
-
GO:0003700
transcription factor activity, sequence-specific DNA binding
GO:0043565
sequence-specific DNA binding
GO:0006355
regulation of transcription, DNA-templated
GO:0005622
intracellular
Chain B was generated from chain A using the biomatrix described in the original PDB file.
2
1
Other
Trp repressor-like
A
The TrpR like protein from Eubacterium eligens ATCC 27750
Eubacterium eligens
MNNKLKTQAVEQLFQAILSLKDLDEAYDFFEDVCTINEILSLSQRFEVAKMLREHRTYLDIAEKTGASTATISRVNRSLNYGNDGYDRVFERLGMLEKESEDNK
104
C4Z2H9
1
104
100%
UniRef90_C4Z2H9
1
104
secondary structure
helix
3
5
secondary structure
helix
8
18
secondary structure
helix
23
33
secondary structure
helix
36
53
secondary structure
helix
58
65
secondary structure
helix
69
80
secondary structure
helix
85
93
pfam
PF01371.16
Trp_repressor
8
94
B
The TrpR like protein from Eubacterium eligens ATCC 27750
Eubacterium eligens
MNNKLKTQAVEQLFQAILSLKDLDEAYDFFEDVCTINEILSLSQRFEVAKMLREHRTYLDIAEKTGASTATISRVNRSLNYGNDGYDRVFERLGMLEKESEDNK
104
C4Z2H9
1
104
100%
UniRef90_C4Z2H9
1
104
secondary structure
helix
3
5
secondary structure
helix
8
18
secondary structure
helix
23
33
secondary structure
helix
36
53
secondary structure
helix
58
65
secondary structure
helix
69
80
secondary structure
helix
85
93
pfam
PF01371.16
Trp_repressor
8
94
The folding and dimerization of the Trp repressor were shown to be linked by both experimental (PMID:10329154, PMID:2223756, PMID:7578063) and computational studies (PMID:10465773).
MF2120018
Putative Trp repressor (Staphylococcus aureus)
3kor
X-ray
1.60
homodimer
Staphylococcus aureus
Lam, R., Vodsedalek, J., Lam, K., Romanov, V., Battaile, K.P., Beletskaya, I., Pai, E.F., Chirgadze, N.Y.
Crystal structure of a putative Trp repressor from Staphylococcus aureus
To be published
-
GO:0003700
transcription factor activity, sequence-specific DNA binding
GO:0043565
sequence-specific DNA binding
GO:0006355
regulation of transcription, DNA-templated
GO:0005622
intracellular
Chains B and C were removed as chains A and D represent the biologically active dimer.
2
1
Other
Trp repressor-like
A
Uncharacterized protein
Staphylococcus aureus
MGSSHHHHHHSSGLVPRGSMQIEKLRGAALDELFDAILTLENREECYQFFDDLCTVNEIQSLSQRLQVAKMIKQGYTYATIEQESGASTATISRVKRSLQWGNDAYTMILDRMNIETNE
119
A0A0H3JS52
1
100
100%
UniRef90_Q49YV2
1
98
secondary structure
helix
3
7
secondary structure
helix
10
20
secondary structure
helix
25
35
secondary structure
helix
38
51
secondary structure
helix
53
57
secondary structure
helix
61
68
secondary structure
helix
72
83
secondary structure
helix
88
88
secondary structure
helix
90
93
secondary structure
helix
95
97
pfam
PF01371.16
Trp_repressor
9
95
D
Uncharacterized protein
Staphylococcus aureus
MGSSHHHHHHSSGLVPRGSMQIEKLRGAALDELFDAILTLENREECYQFFDDLCTVNEIQSLSQRLQVAKMIKQGYTYATIEQESGASTATISRVKRSLQWGNDAYTMILDRMNIETNE
119
A0A0H3JS52
1
100
100%
UniRef90_Q49YV2
1
98
secondary structure
helix
3
7
secondary structure
helix
10
20
secondary structure
helix
25
35
secondary structure
helix
38
51
secondary structure
helix
53
57
secondary structure
helix
61
68
secondary structure
helix
72
84
secondary structure
helix
88
88
secondary structure
helix
90
93
secondary structure
helix
95
97
pfam
PF01371.16
Trp_repressor
9
95
The folding and dimerization of the Trp repressor were shown to be linked by both experimental (PMID:10329154, PMID:2223756, PMID:7578063) and computational studies (PMID:10465773).
MF3300001
Rb C-terminal domain bound to an E2F1-DP1 heterodimer
2aze
X-ray
2.55
heterotrimer
Homo sapiens
16360038
Rubin SM, Gall AL, Zheng N, Pavletich NP
Structure of the Rb C-terminal domain bound to E2F1-DP1: a mechanism for phosphorylation-induced E2F release.
Cell
2005
6
123
1093-106
The retinoblastoma (Rb) protein negatively regulates the G1-S transition by binding to the E2F transcription factors, until cyclin-dependent kinases phosphorylate Rb, causing E2F release. The Rb pocket domain is necessary for E2F binding, but the Rb C-terminal domain (RbC) is also required for growth suppression. Here we demonstrate a high-affinity interaction between RbC and E2F-DP heterodimers shared by all Rb and E2F family members. The crystal structure of an RbC-E2F1-DP1 complex reveals an intertwined heterodimer in which the marked box domains of both E2F1 and DP1 contact RbC. We also demonstrate that phosphorylation of RbC at serines 788 and 795 destabilizes one set of RbC-E2F-DP interactions directly, while phosphorylation at threonines 821 and 826 induces an intramolecular interaction between RbC and the Rb pocket that destabilizes the remaining interactions indirectly. Our findings explain the requirement of RbC for high-affinity E2F binding and growth suppression and establish a mechanism for the regulation of Rb-E2F association by phosphorylation.
GO:0003700
transcription factor activity, sequence-specific DNA binding
GO:0003677
DNA binding
GO:0008134
transcription factor binding
GO:0007049
cell cycle
GO:0006351
transcription, DNA-templated
GO:0045944
positive regulation of transcription from RNA polymerase II promoter
GO:0005667
transcription factor complex
GO:0005654
nucleoplasm
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
3
3
Other
Other
A
Transcription factor Dp-1
Homo sapiens
GEFAQECQNLEVERQRRLERIKQKQSQLQELILQQIAFKNLVQRNRHAEQQASRPPPPNSVIHLPFIIVNTSKKTVIDCSISNDKFEYLFNFDNTFEIHDDIEVLKRMGMACGLESGSCSAEDLKMARSLVPKALEPYVTEMAQGTVGGVFITTA
155
Q14186
196
350
37.8%
UniRef90_Q14186
199
350
secondary structure
helix
199
245
secondary structure
helix
253
255
secondary structure
beta
256
258
secondary structure
beta
262
267
secondary structure
beta
272
276
secondary structure
beta
282
287
secondary structure
beta
291
295
secondary structure
helix
296
302
secondary structure
helix
309
311
secondary structure
helix
316
324
secondary structure
helix
328
339
pfam
PF08781.7
DP
200
338
B
Transcription factor E2F1
Homo sapiens
GSHMGGRLEGLTQDLRQLQESEQQLDHLMNICTTQLRLLSEDTDSQRLAYVTCQDLRSIADPAEQMVMVIKAPPETQLQAVDSSENFQISLKSKQGPIDVFLCPEE
106
Q01094
196
301
24.3%
UniRef90_Q01094
192
301
secondary structure
helix
202
236
secondary structure
helix
238
243
secondary structure
beta
245
247
secondary structure
helix
248
252
secondary structure
beta
260
266
secondary structure
beta
272
277
secondary structure
beta
282
287
secondary structure
beta
294
296
pfam
PF16421.2
E2F_CC-MB
206
299
C
Retinoblastoma-associated protein
Homo sapiens
SRILVSIGESFGTSEKFQKINQMVCNSDRVLKRSAEGSNPPKPLKK
46
P06400
829
874
5%
UniRef90_P06400
829
874
secondary structure
beta
830
834
secondary structure
helix
841
853
pfam
PF08934.7
Rb_C
768
925
The interacting partners have been shown to adopt a stable structure as a result of the interaction (PMID:16360038).
C
The 772-874 region described in IDEAL entry IID00017 covers 100% of the sequence present in the structure.
MF2100006
Rab11 binding domain of Rab11 family interacting protein 2
2k6s
NMR
homodimer
Homo sapiens
19119858
Wei J, Liu Y, Bose K, Henry GD, Baleja JD
Disorder and structure in the Rab11 binding domain of Rab11 family interacting protein 2.
Biochemistry
2009
3
48
549-57
Rab11 plays a central role in plasma membrane recycling which returns cellular receptors for reuse at the cell surface. A recently identified family of Rab11 interacting proteins (FIP) includes FIP2. The C-terminal region of FIP2 is essential for colocalization with Rab11 on early endosomes and for enabling formation of higher-order oligomers. Rab11 binding and oligomerization of FIP2 are separable. Here we have determined the three-dimensional structure of the 40-residue coiled-coil oligomerization domain of FIP2 in the absence of Rab11 using NMR methods. The N-terminal half showed strong NOE cross-peaks and well-dispersed NMR resonances, whereas the C-terminal half had fewer NOE cross-peaks and less chemical shift dispersion. The 10 C-terminal residues were mostly disordered. The final structures of the dimer had favorable Ramachandran angles and a root-mean-square deviation of 0.59 +/- 0.13 A over superimposed backbone residues. The structure allows a comparison to a structure of FIP2 in complex with Rab11 that was determined crystallographically. In complex with Rab11, the C-terminal residues are not disordered but have a helical structure that predicts residual dipolar coupling constants that are incompatible with those measured on the unbound FIP2. In both structures, a histidine residue is found at the normally hydrophobic position of the heptad repeat of the coiled coil, and here we show its ionization destabilizes the coiled-coil structure. Together, these data allow us to build a model in which the binding of FIP family proteins to Rab11 can be described in terms of conformational changes and that suggests new modes of regulation.
GO:0019901
protein kinase binding
GO:0017137
Rab GTPase binding
GO:0042803
protein homodimerization activity
GO:0045055
regulated exocytosis
GO:0030010
establishment of cell polarity
GO:0035773
insulin secretion involved in cellular response to glucose stimulus
GO:0003091
renal water homeostasis
GO:0005654
nucleoplasm
GO:0005886
plasma membrane
GO:0030659
cytoplasmic vesicle membrane
GO:0055038
recycling endosome membrane
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Coils and zippers
Coiled coil (dimeric)
A
Rab11 family-interacting protein 2
Homo sapiens
GSLTYEEVLQELVKHKELLRRKDTHIRELEDYIDNLLVRVM
41
Q7L804
449
489
8%
UniRef90_Q7L804
450
489
secondary structure
helix
453
485
pfam
PF09457.7
RBD-FIP
452
499
B
Rab11 family-interacting protein 2
Homo sapiens
GSLTYEEVLQELVKHKELLRRKDTHIRELEDYIDNLLVRVM
41
Q7L804
449
489
8%
UniRef90_Q7L804
450
489
secondary structure
helix
453
485
pfam
PF09457.7
RBD-FIP
452
499
The subunits in the structure are bound via coiled coil interactions (PMID:19119858). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
3tso
4c4p
MF4100003
p53 tetramerization domain (human)
2j0z
NMR
homotetramer (dimer of dimers)
Homo sapiens
18076077
Mora P, Carbajo RJ, Pineda-Lucena A, Sánchez del Pino MM, Pérez-Payá E
Solvent-exposed residues located in the beta-sheet modulate the stability of the tetramerization domain of p53--a structural and combinatorial approach.
Proteins
2008
4
71
1670-85
The role of hydrophobic amino acids in the formation of hydrophobic cores as one of the major driving forces in protein folding has been extensively studied. However, the implication of neutral solvent-exposed amino acids is less clear and available information is scarce. We have used a combinatorial approach to study the structural relevance of three solvent-exposed residues (Tyr(327), Thr(329), and Gln(331)) located in thebeta-sheet of the tetramerization domain of the tumor suppressor p53 (p53TD). A conformationally defined peptide library was designed where these three positions were randomized. The library was screened for tetramer stability. A set of p53TD mutants containing putative stabilizing or destabilizing residue combinations was synthesized for a thermodynamic characterization. Unfolding experiments showed a wide range of stabilities, with T(m) values between 27 and 83 degrees C. Wild type p53TD and some highly destabilized and stabilized mutants were further characterized. Thermodynamic and biophysical data indicated that these proteins were folded tetramers, with the same overall structure, in equilibrium with unfolded monomers. An NMR study confirmed that the main structural features of p53TD are conserved in all the mutants analyzed. The thermodynamic stability of the different p53TD mutants showed a strong correlation with parameters that favor formation and stabilization of the beta-sheet. We propose that stabilization through hydrophobic interactions of key secondary structure elements might be the underlying mechanism for the strong influence of solvent-exposed residues in the stability of p53TD.
GO:0002039
p53 binding
GO:0005507
copper ion binding
GO:0001228
transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding
GO:0002020
protease binding
GO:0051721
protein phosphatase 2A binding
GO:0005524
ATP binding
GO:0043621
protein self-association
GO:0030971
receptor tyrosine kinase binding
GO:0003684
damaged DNA binding
GO:0035035
histone acetyltransferase binding
GO:0046982
protein heterodimerization activity
GO:0047485
protein N-terminus binding
GO:0031625
ubiquitin protein ligase binding
GO:0001085
RNA polymerase II transcription factor binding
GO:0001046
core promoter sequence-specific DNA binding
GO:0042802
identical protein binding
GO:0051087
chaperone binding
GO:0003682
chromatin binding
GO:0008270
zinc ion binding
GO:0048512
circadian behavior
GO:0051974
negative regulation of telomerase activity
GO:0007265
Ras protein signal transduction
GO:0030308
negative regulation of cell growth
GO:0043153
entrainment of circadian clock by photoperiod
GO:0006289
nucleotide-excision repair
GO:0006284
base-excision repair
GO:0043066
negative regulation of apoptotic process
GO:2000379
positive regulation of reactive oxygen species metabolic process
GO:0031497
chromatin assembly
GO:1902749
regulation of cell cycle G2/M phase transition
GO:1901796
regulation of signal transduction by p53 class mediator
GO:0048147
negative regulation of fibroblast proliferation
GO:0090399
replicative senescence
GO:0000733
DNA strand renaturation
GO:1900740
positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
GO:0016925
protein sumoylation
GO:0006978
DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator
GO:0090200
positive regulation of release of cytochrome c from mitochondria
GO:0006977
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
GO:0035690
cellular response to drug
GO:0030154
cell differentiation
GO:1900119
positive regulation of execution phase of apoptosis
GO:0016032
viral process
GO:0008283
cell proliferation
GO:0010165
response to X-ray
GO:0071456
cellular response to hypoxia
GO:2001244
positive regulation of intrinsic apoptotic signaling pathway
GO:0010332
response to gamma radiation
GO:0051262
protein tetramerization
GO:0071479
cellular response to ionizing radiation
GO:0031065
positive regulation of histone deacetylation
GO:0008340
determination of adult lifespan
GO:0034644
cellular response to UV
GO:0034613
cellular protein localization
GO:0090403
oxidative stress-induced premature senescence
GO:0046827
positive regulation of protein export from nucleus
GO:0042149
cellular response to glucose starvation
GO:0006983
ER overload response
GO:0006366
transcription from RNA polymerase II promoter
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0043525
positive regulation of neuron apoptotic process
GO:0000122
negative regulation of transcription from RNA polymerase II promoter
GO:0032461
positive regulation of protein oligomerization
GO:0097252
oligodendrocyte apoptotic process
GO:1990440
positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress
GO:0042771
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:0046677
response to antibiotic
GO:0050731
positive regulation of peptidyl-tyrosine phosphorylation
GO:0051097
negative regulation of helicase activity
GO:0007050
cell cycle arrest
GO:0070245
positive regulation of thymocyte apoptotic process
GO:0016363
nuclear matrix
GO:0005730
nucleolus
GO:0005759
mitochondrial matrix
GO:0005783
endoplasmic reticulum
GO:0005657
replication fork
GO:0016605
PML body
GO:0005829
cytosol
GO:0043234
protein complex
GO:0000790
nuclear chromatin
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
1
Other
p53 tetramerization
A
Cellular tumor antigen p53
Homo sapiens
EYFTLQIRGRERFEMFRELNEALELKDAQAG
31
P04637
326
356
7.9%
UniRef90_P04637
326
356
secondary structure
beta
328
332
secondary structure
helix
335
354
pfam
PF07710.8
P53_tetramer
319
358
B
Cellular tumor antigen p53
Homo sapiens
EYFTLQIRGRERFEMFRELNEALELKDAQAG
31
P04637
326
356
7.9%
UniRef90_P04637
326
356
secondary structure
beta
328
332
secondary structure
helix
335
354
pfam
PF07710.8
P53_tetramer
319
358
C
Cellular tumor antigen p53
Homo sapiens
EYFTLQIRGRERFEMFRELNEALELKDAQAG
31
P04637
326
356
7.9%
UniRef90_P04637
326
356
secondary structure
beta
328
332
secondary structure
helix
335
353
pfam
PF07710.8
P53_tetramer
319
358
D
Cellular tumor antigen p53
Homo sapiens
EYFTLQIRGRERFEMFRELNEALELKDAQAG
31
P04637
326
356
7.9%
UniRef90_P04637
326
356
secondary structure
beta
328
332
secondary structure
helix
335
354
pfam
PF07710.8
P53_tetramer
319
358
The tetramerization domain of p53 exhibits a four-helix bundle structure bound by hydrophobic and electrostatic interactions (PMID:8023159). The tetramer is formed as a dimer of dimers and follows a two state folding and binding process, demonstrated in several chemical and thermal denaturation/refolding experiments (PMID:9582268, PMID:18410249, PMID:19913028).
1a1u
1aie
1c26
1hs5
2j10
2j11
1olg
1olh
1pes
1pet
1sae
1saf
1sak
1sal
3sak
MF4110007
p53 tetramerization domain (Danio rerio)
4d1l
X-ray
1.97
homotetramer (dimer of dimers)
Danio rerio
25185827
Joerger AC, Wilcken R, Andreeva A
Tracing the Evolution of the p53 Tetramerization Domain.
Structure
2014
9
22
1301-10
The tetrameric transcription factors p53, p63, and p73 evolved from a common ancestor and play key roles in tumor suppression and development. Surprisingly, p63 and p73 require a second helix in their tetramerization domain for the formation of stable tetramers that is absent in human p53, raising questions about the evolutionary processes leading to diversification. Here we determined the crystal structure of the zebrafish p53 tetramerization domain, which contains a second helix, reminiscent of p63 and p73, combined with p53-like features. Through comprehensive phylogenetic analyses, we systematically traced the evolution of vertebrate p53 family oligomerization domains back to the beginning of multicellular life. We provide evidence that their last common ancestor also had an extended p63/p73-like domain and pinpoint evolutionary events that shaped this domain during vertebrate radiation. Domain compaction and transformation of a structured into a flexible, intrinsically disordered region may have contributed to the expansion of the human p53 interactome.
GO:0003700
transcription factor activity, sequence-specific DNA binding
GO:0044212
transcription regulatory region DNA binding
GO:0046872
metal ion binding
GO:0006355
regulation of transcription, DNA-templated
GO:0006915
apoptotic process
GO:0007049
cell cycle
GO:0051262
protein tetramerization
GO:0006351
transcription, DNA-templated
GO:0005737
cytoplasm
GO:0005634
nucleus
Chains A and B were removed as chains C, D, E and F represent the biologically relevant tetramer.
4
1
Other
p53 tetramerization
C
Cellular tumor antigen p53
Danio rerio
GGSEEIFTLQVRGRERYEILKKLNDSLELSDVVPASDAEKYRQKFMTK
48
G1K2L5
299
346
12.8%
UniRef90_P79734
301
345
secondary structure
beta
304
310
secondary structure
helix
312
330
secondary structure
helix
333
339
pfam
PF07710.8
P53_tetramer
294
335
D
Cellular tumor antigen p53
Danio rerio
GGSEEIFTLQVRGRERYEILKKLNDSLELSDVVPASDAEKYRQKFMTK
48
G1K2L5
299
346
12.8%
UniRef90_P79734
301
345
secondary structure
beta
303
309
secondary structure
helix
311
327
secondary structure
helix
332
340
pfam
PF07710.8
P53_tetramer
294
335
E
Cellular tumor antigen p53
Danio rerio
GGSEEIFTLQVRGRERYEILKKLNDSLELSDVVPASDAEKYRQKFMTK
48
G1K2L5
299
346
12.8%
UniRef90_P79734
301
345
secondary structure
beta
304
310
secondary structure
helix
312
330
secondary structure
helix
333
340
pfam
PF07710.8
P53_tetramer
294
335
F
Cellular tumor antigen p53
Danio rerio
GGSEEIFTLQVRGRERYEILKKLNDSLELSDVVPASDAEKYRQKFMTK
48
G1K2L5
299
346
12.8%
UniRef90_P79734
301
345
secondary structure
beta
304
310
secondary structure
helix
312
330
secondary structure
helix
333
335
pfam
PF07710.8
P53_tetramer
294
335
The tetramerization domain of p53 exhibits a four-helix bundle structure bound by hydrophobic and electrostatic interactions (PMID:8023159). The tetramer is formed as a dimer of dimers and follows a two state folding and binding process, demonstrated in several chemical and thermal denaturation/refolding experiments (PMID:9582268, PMID:18410249, PMID:19913028).
4d1m
4cz5
4cz6
4cz7
MF4100004
p63 tetramerization domain (human)
3zy1
X-ray
2.15
homotetramer (dimer of dimers)
Homo sapiens
22100306
Natan E, Joerger AC
Structure and kinetic stability of the p63 tetramerization domain.
J. Mol. Biol.
2012
3
415
503-13
The p53 family of transcription factors--comprising p53, p63 and p73--plays an important role in tumor prevention and development. Essential to their function is the formation of tetramers, allowing cooperative binding to their DNA response elements. We solved crystal structures of the human p63 tetramerization domain, showing that p63 forms a dimer of dimers with D₂ symmetry composed of highly intertwined monomers. The primary dimers are formed via an intramolecular β-sheet and hydrophobic helix packing (H1), a hallmark of all p53 family members. Like p73, but unlike p53, p63 requires a second helix (H2) to stabilize the architecture of the tetramer. In order to investigate the impact of structural differences on tetramer stability, we measured the subunit exchange reaction of p53 family homotetramers by nanoflow electrospray mass spectrometry. There were differences in both the kinetics and the pattern of the exchange reaction, with the p53 and p63 tetramers exhibiting much faster exchange kinetics than p73. The structural similarity between p63 and p73 rationalizes previous observations that p63 and p73 form mixed tetramers, and the kinetic data reveal the dissociation of the p73 homotetramers as the rate-limiting step for heterotetramer formation. Differential stability of the tetramers may play an important role in the cross talk between different isoforms and regulation of p53, p63 and p73 function in the cell cycle.
GO:0003690
double-stranded DNA binding
GO:0001077
transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0002039
p53 binding
GO:0003684
damaged DNA binding
GO:0050699
WW domain binding
GO:0043565
sequence-specific DNA binding
GO:0044212
transcription regulatory region DNA binding
GO:0000989
transcription factor activity, transcription factor binding
GO:0046872
metal ion binding
GO:0003682
chromatin binding
GO:0042802
identical protein binding
GO:0043066
negative regulation of apoptotic process
GO:0060197
cloacal septation
GO:0061436
establishment of skin barrier
GO:1902808
positive regulation of cell cycle G1/S phase transition
GO:0031069
hair follicle morphogenesis
GO:2000381
negative regulation of mesoderm development
GO:0010482
regulation of epidermal cell division
GO:0002053
positive regulation of mesenchymal cell proliferation
GO:0060157
urinary bladder development
GO:0051289
protein homotetramerization
GO:0030859
polarized epithelial cell differentiation
GO:0048807
female genitalia morphogenesis
GO:0043281
regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0010259
multicellular organism aging
GO:0007219
Notch signaling pathway
GO:0002064
epithelial cell development
GO:0006978
DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator
GO:0001302
replicative cell aging
GO:0048485
sympathetic nervous system development
GO:0001501
skeletal system development
GO:1900740
positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
GO:0030326
embryonic limb morphogenesis
GO:0045669
positive regulation of osteoblast differentiation
GO:0051402
neuron apoptotic process
GO:0043616
keratinocyte proliferation
GO:1901796
regulation of signal transduction by p53 class mediator
GO:0043589
skin morphogenesis
GO:0045617
negative regulation of keratinocyte differentiation
GO:0045944
positive regulation of transcription from RNA polymerase II promoter
GO:0006366
transcription from RNA polymerase II promoter
GO:0031571
mitotic G1 DNA damage checkpoint
GO:0060529
squamous basal epithelial stem cell differentiation involved in prostate gland acinus development
GO:0010481
epidermal cell division
GO:0036342
post-anal tail morphogenesis
GO:0000122
negative regulation of transcription from RNA polymerase II promoter
GO:0030216
keratinocyte differentiation
GO:0010838
positive regulation of keratinocyte proliferation
GO:0010165
response to X-ray
GO:0010332
response to gamma radiation
GO:0007499
ectoderm and mesoderm interaction
GO:0006338
chromatin remodeling
GO:0034644
cellular response to UV
GO:0007283
spermatogenesis
GO:0048745
smooth muscle tissue development
GO:0043523
regulation of neuron apoptotic process
GO:0060513
prostatic bud formation
GO:2000773
negative regulation of cellular senescence
GO:0042771
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:2000271
positive regulation of fibroblast apoptotic process
GO:0042475
odontogenesis of dentin-containing tooth
GO:0001736
establishment of planar polarity
GO:0009954
proximal/distal pattern formation
GO:0045747
positive regulation of Notch signaling pathway
GO:0005667
transcription factor complex
GO:0005739
mitochondrion
GO:0005791
rough endoplasmic reticulum
GO:0005654
nucleoplasm
GO:0030425
dendrite
GO:0000790
nuclear chromatin
GO:0005829
cytosol
Chains B, C and D were generated from chain A using the biomatrices described in the original PDB file.
4
1
Other
p53 tetramerization
A
Tumor protein 63
Homo sapiens
GSDELLYLPVRGRETYEMLLKIKESLELMQYLPQHTIETYRQQQQQ
46
Q9H3D4
396
441
6.8%
UniRef90_Q9H3D4
398
436
secondary structure
beta
400
406
secondary structure
helix
408
426
secondary structure
helix
429
436
pfam
PF07710.8
P53_tetramer
391
431
B
Tumor protein 63
Homo sapiens
GSDELLYLPVRGRETYEMLLKIKESLELMQYLPQHTIETYRQQQQQ
46
Q9H3D4
396
441
6.8%
UniRef90_Q9H3D4
398
436
secondary structure
beta
400
406
secondary structure
helix
408
426
secondary structure
helix
429
436
pfam
PF07710.8
P53_tetramer
391
431
C
Tumor protein 63
Homo sapiens
GSDELLYLPVRGRETYEMLLKIKESLELMQYLPQHTIETYRQQQQQ
46
Q9H3D4
396
441
6.8%
UniRef90_Q9H3D4
398
436
secondary structure
beta
400
406
secondary structure
helix
408
426
secondary structure
helix
429
436
pfam
PF07710.8
P53_tetramer
391
431
D
Tumor protein 63
Homo sapiens
GSDELLYLPVRGRETYEMLLKIKESLELMQYLPQHTIETYRQQQQQ
46
Q9H3D4
396
441
6.8%
UniRef90_Q9H3D4
398
436
secondary structure
beta
400
406
secondary structure
helix
408
426
secondary structure
helix
429
436
pfam
PF07710.8
P53_tetramer
391
431
p63 is a member of the p53 protein family. The tetramerization region of p53, p63 and p73 are closely homologous to each other, having very similar sequences, structures and biological functions (PMID:25185827, PMID:18289041, PMID:20379196), all containing the same Pfam domain (PF07710). The tetramerization domain of p53 exhibits a four-helix bundle structure bound by hydrophobic and electrostatic interactions (PMID:8023159). The tetramer is formed as a dimer of dimers and follows a two state folding and binding process, demonstrated in several chemical and thermal denaturation/refolding experiments (PMID:9582268, PMID:18410249, PMID:19913028).
3zy0
4a9z
MF4100005
p73 tetramerization domain (human)
2kby
NMR
homotetramer (dimer of dimers)
Homo sapiens
19763140
Coutandin D, Löhr F, Niesen FH, Ikeya T, Weber TA, Schäfer B, Zielonka EM, Bullock AN, Yang A, Güntert P, Knapp S, McKeon F, Ou HD, Dötsch V
Conformational stability and activity of p73 require a second helix in the tetramerization domain.
Cell Death Differ.
2009
12
16
1582-9
p73 and p63, the two ancestral members of the p53 family, are involved in neurogenesis, epithelial stem cell maintenance and quality control of female germ cells. The highly conserved oligomerization domain (OD) of tumor suppressor p53 is essential for its biological functions, and its structure was believed to be the prototype for all three proteins. However, we report that the ODs of p73 and p63 differ from the OD of p53 by containing an additional alpha-helix that is not present in the structure of the p53 OD. Deletion of this helix causes a dissociation of the OD into dimers; it also causes conformational instability and reduces the transcriptional activity of p73. Moreover, we show that ODs of p73 and p63 strongly interact and that a large number of different heterotetramers are supported by the additional helix. Detailed analysis shows that the heterotetramer consisting of two homodimers is thermodynamically more stable than the two homotetramers. No heterooligomerization between p53 and the p73/p63 subfamily was observed, supporting the notion of functional orthogonality within the p53 family.
GO:0003684
damaged DNA binding
GO:0001077
transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0002039
p53 binding
GO:0008134
transcription factor binding
GO:0000978
RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0042802
identical protein binding
GO:0003682
chromatin binding
GO:0046872
metal ion binding
GO:0019901
protein kinase binding
GO:0060044
negative regulation of cardiac muscle cell proliferation
GO:0042493
response to drug
GO:1901796
regulation of signal transduction by p53 class mediator
GO:0006298
mismatch repair
GO:0043524
negative regulation of neuron apoptotic process
GO:0006978
DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator
GO:0001822
kidney development
GO:1900740
positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
GO:0048714
positive regulation of oligodendrocyte differentiation
GO:0071158
positive regulation of cell cycle arrest
GO:0042771
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:0000187
activation of MAPK activity
GO:0010243
response to organonitrogen compound
GO:0045665
negative regulation of neuron differentiation
GO:0043508
negative regulation of JUN kinase activity
GO:0007050
cell cycle arrest
GO:0034644
cellular response to UV
GO:0051262
protein tetramerization
GO:0010332
response to gamma radiation
GO:0010165
response to X-ray
GO:0016032
viral process
GO:0000122
negative regulation of transcription from RNA polymerase II promoter
GO:0031571
mitotic G1 DNA damage checkpoint
GO:0006366
transcription from RNA polymerase II promoter
GO:0045944
positive regulation of transcription from RNA polymerase II promoter
GO:0005794
Golgi apparatus
GO:0005739
mitochondrion
GO:0030054
cell junction
GO:0005667
transcription factor complex
GO:0005829
cytosol
GO:0000785
chromatin
GO:0005654
nucleoplasm
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
1
Other
p53 tetramerization
A
Tumor protein p73
Homo sapiens
GSDEDTYYLQVRGRENFEILMKLKESLELMELVPQPLVDSYRQQQQLLQR
50
O15350
349
398
7.9%
UniRef90_O15350
351
389
secondary structure
beta
354
360
secondary structure
helix
362
377
secondary structure
helix
383
389
pfam
PF07710.8
P53_tetramer
345
384
B
Tumor protein p73
Homo sapiens
GSDEDTYYLQVRGRENFEILMKLKESLELMELVPQPLVDSYRQQQQLLQR
50
O15350
349
398
7.9%
UniRef90_O15350
351
389
secondary structure
beta
354
360
secondary structure
helix
362
377
secondary structure
helix
383
389
pfam
PF07710.8
P53_tetramer
345
384
C
Tumor protein p73
Homo sapiens
GSDEDTYYLQVRGRENFEILMKLKESLELMELVPQPLVDSYRQQQQLLQR
50
O15350
349
398
7.9%
UniRef90_O15350
351
389
secondary structure
beta
354
360
secondary structure
helix
362
377
secondary structure
helix
383
389
pfam
PF07710.8
P53_tetramer
345
384
D
Tumor protein p73
Homo sapiens
GSDEDTYYLQVRGRENFEILMKLKESLELMELVPQPLVDSYRQQQQLLQR
50
O15350
349
398
7.9%
UniRef90_O15350
351
389
secondary structure
beta
354
360
secondary structure
helix
362
377
secondary structure
helix
383
389
pfam
PF07710.8
P53_tetramer
345
384
p73 is a member of the p53 protein family. The tetramerization region of p53, p63 and p73 are closely homologous to each other, having very similar sequences, structures and biological functions (PMID:25185827, PMID:18289041, PMID:20379196), all containing the same Pfam domain (PF07710). The tetramerization domain of p53 exhibits a four-helix bundle structure bound by hydrophobic and electrostatic interactions (PMID:8023159). The tetramer is formed as a dimer of dimers and follows a two state folding and binding process, demonstrated in several chemical and thermal denaturation/refolding experiments (PMID:9582268, PMID:18410249, PMID:19913028).
2wqi
2wtt
2wqj
5hob
5hoc
MF2140005
DNA binding domain of the E2 protein (Human papillomavirus type 16)
1r8p
NMR
homodimer
Human papillomavirus type 16
15702528
Nadra AD, Eliseo T, Mok YK, Almeida CL, Bycroft M, Paci M, de Prat-Gay G, Cicero DO
Solution structure of the HPV-16 E2 DNA binding domain, a transcriptional regulator with a dimeric beta-barrel fold.
J. Biomol. NMR
2004
2
30
211-4
GO:0003700
transcription factor activity, sequence-specific DNA binding
GO:0005515
protein binding
GO:0000166
nucleotide binding
GO:0003677
DNA binding
GO:0006355
regulation of transcription, DNA-templated
GO:0039693
viral DNA genome replication
GO:0006351
transcription, DNA-templated
GO:0006275
regulation of DNA replication
GO:0044163
host cytoskeleton
GO:0042025
host cell nucleus
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Other
E2 dimer
A
Regulatory protein E2
Human papillomavirus type 16
MTPIVHLKGDANTLKCLRYRFKKHCTLYTAVSSTWHWTGHNVKHKSAIVTLTYDSEWQRDQFLSQVKIPKTITVSTGFMSI
81
P03120
285
365
22.2%
UniRef90_P03120
286
365
secondary structure
beta
286
292
secondary structure
helix
295
307
secondary structure
beta
314
315
secondary structure
beta
319
319
secondary structure
beta
332
336
secondary structure
helix
340
349
secondary structure
beta
360
364
pfam
PF00511.14
PPV_E2_C
287
363
B
Regulatory protein E2
Human papillomavirus type 16
MTPIVHLKGDANTLKCLRYRFKKHCTLYTAVSSTWHWTGHNVKHKSAIVTLTYDSEWQRDQFLSQVKIPKTITVSTGFMSI
81
P03120
285
365
22.2%
UniRef90_P03120
286
365
secondary structure
beta
286
292
secondary structure
helix
295
307
secondary structure
beta
314
315
secondary structure
beta
319
319
secondary structure
beta
332
336
secondary structure
helix
340
349
secondary structure
beta
360
364
pfam
PF00511.14
PPV_E2_C
287
363
The DNA binding domain of E2 was shown to exhibit a two-state concerted unfolding and dissociation in denaturation/renaturation experiments (PMID:8745409, PMID:8756330).
2q79
1zzf
1by9
3mi7
MF2140006
DNA binding domain of the E2 protein (Human papillomavirus type 18)
1f9f
X-ray
1.90
homodimer
Human papillomavirus type 18
10906136
Kim SS, Tam JK, Wang AF, Hegde RS
The structural basis of DNA target discrimination by papillomavirus E2 proteins.
J. Biol. Chem.
2000
40
275
31245-54
The papillomavirus E2 proteins regulate the transcription of all papillomavirus genes and are necessary for viral DNA replication. Disruption of the E2 gene is commonly associated with malignancy in cervical carcinoma, indicating that E2 has a role in regulating tumor progression. Although the E2 proteins from all characterized papillomaviruses bind specifically to the same 12-base pair DNA sequence, the cancer-associated human papillomavirus E2 proteins display a unique ability to detect DNA flexibility and intrinsic curvature. To understand the structural basis for this phenomenon, we have determined the crystal structures of the human papillomavirus-18 E2 DNA-binding domain and its complexes with high and low affinity binding sites. The E2 protein is a dimeric beta-barrel and the E2-DNA interaction is accompanied by a large deformation of the DNA as it conforms to the E2 surface. DNA conformation and E2-DNA contacts are similar in both high and low affinity complexes. The differences in affinity correlate with the flexibility of the DNA sequence. Preferences of E2 proteins from different papillomavirus strains for flexible or prevent DNA targets correlate with the distribution of positive charge on their DNA interaction surfaces, suggesting a role for electrostatic forces in the recognition of DNA deformability.
GO:0003677
DNA binding
GO:0003700
transcription factor activity, sequence-specific DNA binding
GO:0005515
protein binding
GO:0000166
nucleotide binding
GO:0006275
regulation of DNA replication
GO:0039693
viral DNA genome replication
GO:0006351
transcription, DNA-templated
GO:0006355
regulation of transcription, DNA-templated
GO:0042025
host cell nucleus
GO:0044163
host cytoskeleton
Chains C and D were removed as chains A and B represent the biologically active dimer.
2
1
Other
E2 dimer
A
Regulatory protein E2
Human papillomavirus type 18
GSHMTPIIHLKGDRNSLKCLRYRLRKHSDHYRDISSTWHWTGAGNEKTGILTVTYHSETQRTKFLNTVAIPDSVQILVGYMTM
83
P06790
283
365
22.7%
UniRef90_P06790
287
365
secondary structure
beta
286
295
secondary structure
helix
296
309
secondary structure
beta
315
317
secondary structure
beta
320
320
secondary structure
beta
330
336
secondary structure
helix
340
349
secondary structure
beta
357
364
pfam
PF00511.14
PPV_E2_C
288
363
B
Regulatory protein E2
Human papillomavirus type 18
GSHMTPIIHLKGDRNSLKCLRYRLRKHSDHYRDISSTWHWTGAGNEKTGILTVTYHSETQRTKFLNTVAIPDSVQILVGYMTM
83
P06790
283
365
22.7%
UniRef90_P06790
287
365
secondary structure
beta
286
295
secondary structure
helix
296
306
secondary structure
helix
310
312
secondary structure
beta
315
316
secondary structure
beta
320
320
secondary structure
beta
322
322
secondary structure
beta
330
336
secondary structure
helix
340
349
secondary structure
beta
357
364
pfam
PF00511.14
PPV_E2_C
288
363
The DNA binding domain of E2 was shown to exhibit a two-state concerted unfolding and dissociation in denaturation/renaturation experiments (PMID:8745409, PMID:8756330).
1jj4
MF2140007
DNA binding domain of the E2 protein (Human papillomavirus type 31)
1dhm
NMR
homodimer
Human papillomavirus type 31
8652551
Liang H, Petros AM, Meadows RP, Yoon HS, Egan DA, Walter K, Holzman TF, Robins T, Fesik SW
Solution structure of the DNA-binding domain of a human papillomavirus E2 protein: evidence for flexible DNA-binding regions.
Biochemistry
1996
7
35
2095-103
The three-dimensional structure of the DNA-binding domain of the E2 protein from human papillomavirus-31 was determined by using multidimensional heteronuclear nuclear magnetic resonance (NMR) spectroscopy. A total of 1429 NMR-derived distance and dihedral angle restraints were obtained for each of the 83-residue subunits of this symmetric dimer. The average root mean square deviations of 20 structures calculated using a distance geometry-simulated annealing protocol are 0.59 and 0.90 angstroms for the backbone and all heavy atoms, respectively, for residues 2-83. The structure of the human virus protein free in solution consists of an eight-stranded beta-barrel and two pairs of alpha-helices. Although the overall fold of the protein is similar to the crystal structure of the bovine papillomavirus-1 E2 protein when complexed to DNA, several small but interesting differences were observed between these two structures at the subunit interface. In addition, a beta-hairpin that contacts DNA in the crystal structure of the protein-DNA complex is disordered in the NMR structures, and steady-state 1H-15N heteronuclear NOE measurements indicate that this region is highly mobile in the absence of DNA. The recognition helix also appears to be flexible, as evidenced by fast amide exchange rates. This phenomenon has also been observed for a number of other DNA-binding proteins and may constitute a common theme in protein/DNA recognition.
GO:0003677
DNA binding
GO:0003700
transcription factor activity, sequence-specific DNA binding
GO:0005515
protein binding
GO:0000166
nucleotide binding
GO:0006355
regulation of transcription, DNA-templated
GO:0006275
regulation of DNA replication
GO:0039693
viral DNA genome replication
GO:0006351
transcription, DNA-templated
GO:0042025
host cell nucleus
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Other
E2 dimer
A
Regulatory protein E2
Human papillomavirus type 31
MATTPIIHLKGDANILKCLRYRLSKYKQLYEQVSSTWHWTCTDGKHKNAIVTLTYISTSQRDDFLNTVKIPNTVSVSTGYMTI
83
P17383
290
372
22.3%
UniRef90_P17383
291
372
secondary structure
beta
294
299
secondary structure
helix
302
314
secondary structure
beta
321
322
secondary structure
beta
326
326
secondary structure
beta
339
343
secondary structure
helix
347
356
secondary structure
beta
364
369
pfam
PF00511.14
PPV_E2_C
294
370
B
Regulatory protein E2
Human papillomavirus type 31
MATTPIIHLKGDANILKCLRYRLSKYKQLYEQVSSTWHWTCTDGKHKNAIVTLTYISTSQRDDFLNTVKIPNTVSVSTGYMTI
83
P17383
290
372
22.3%
UniRef90_P17383
291
372
secondary structure
beta
294
299
secondary structure
helix
302
314
secondary structure
beta
321
322
secondary structure
beta
326
326
secondary structure
beta
339
343
secondary structure
helix
347
356
secondary structure
beta
364
369
pfam
PF00511.14
PPV_E2_C
294
370
The DNA binding domain of E2 was shown to exhibit a two-state concerted unfolding and dissociation in denaturation/renaturation experiments (PMID:8745409, PMID:8756330).
1a7g
MF2140008
DNA binding domain of the E2 protein (Human papillomavirus type 6a)
2aye
X-ray
2.30
homodimer
Human papillomavirus type 6a
16914454
Hooley E, Fairweather V, Clarke AR, Gaston K, Brady RL
The recognition of local DNA conformation by the human papillomavirus type 6 E2 protein.
Nucleic Acids Res.
2006
14
34
3897-908
The E2 proteins are transcription/replication factors from papillomaviruses. Human papillomaviruses (HPVs) can be broadly divided in two groups; low-risk HPV subtypes cause benign warts while high-risk HPVs give rise to cervical cancer. Although a range of crystal structures of E2 DNA-binding domains (DBD) from both high- and low-risk HPV subtypes have been reported previously, structures of E2 DBD:DNA complexes have only been available for high-risk HPV18 and bovine papillomavirus (BPV1). In the present study we report the unliganded and DNA complex structures of the E2 DBD from the low-risk HPV6. As in the previous E2-DNA structures, complex formation results in considerable bending of the DNA, which is facilitated by sequences with A:T-rich spacers that adopt a pre-bent conformation. The low-risk HPV6 E2-DNA complex differs from the earlier structures in that minimal deformation of the protein accompanies complex formation. Stopped-flow kinetic studies confirm that both high- and low-risk E2 proteins adapt their structures on binding to DNA, although this is achieved more readily for HPV6 E2. It therefore appears that the higher selectivity of the HPV6 E2 protein may arise from its limited molecular adaptability, a property that might distinguish the behaviour of E2 proteins from high- and low-risk HPV subtypes.
GO:0003677
DNA binding
GO:0000166
nucleotide binding
GO:0003700
transcription factor activity, sequence-specific DNA binding
GO:0006355
regulation of transcription, DNA-templated
GO:0006275
regulation of DNA replication
GO:0006351
transcription, DNA-templated
GO:0039693
viral DNA genome replication
GO:0042025
host cell nucleus
Chains C, D, E and F were removed as chains A and B represent the biologically active dimer.
2
1
Other
E2 dimer
A
Regulatory protein E2
Human papillomavirus type 6a
SSATPIVQFQGESNCLKCFRYRLNDKHRHLFDLISSTWHWASPKAPHKHAIVTVTYHSEEQRQQFLNVVKIPPTIRHKLGFMSMHLL
87
Q84294
282
368
23.6%
UniRef90_Q84294
282
368
secondary structure
beta
284
292
secondary structure
helix
294
305
secondary structure
helix
307
307
secondary structure
helix
309
311
secondary structure
beta
315
316
secondary structure
beta
319
319
secondary structure
beta
321
321
secondary structure
beta
331
336
secondary structure
helix
340
349
secondary structure
beta
357
364
secondary structure
helix
365
367
pfam
PF00511.14
PPV_E2_C
286
363
B
Regulatory protein E2
Human papillomavirus type 6a
SSATPIVQFQGESNCLKCFRYRLNDKHRHLFDLISSTWHWASPKAPHKHAIVTVTYHSEEQRQQFLNVVKIPPTIRHKLGFMSMHLL
87
Q84294
282
368
23.6%
UniRef90_Q84294
282
368
secondary structure
beta
284
292
secondary structure
helix
294
305
secondary structure
helix
307
307
secondary structure
helix
309
311
secondary structure
beta
315
316
secondary structure
beta
319
319
secondary structure
beta
321
321
secondary structure
beta
331
336
secondary structure
helix
340
349
secondary structure
beta
357
364
secondary structure
helix
365
367
pfam
PF00511.14
PPV_E2_C
286
363
The DNA binding domain of E2 was shown to exhibit a two-state concerted unfolding and dissociation in denaturation/renaturation experiments (PMID:8745409, PMID:8756330).
2ayb
2ayg
1r8h
MF2140009
DNA binding domain of the E2 protein (Bovine papillomavirus type 1)
1dbd
NMR
homodimer
Bovine papillomavirus type 1
10587434
Veeraraghavan S, Mello CC, Androphy EJ, Baleja JD
Structural correlates for enhanced stability in the E2 DNA-binding domain from bovine papillomavirus.
Biochemistry
1999
49
38
16115-24
Papillomaviral E2 proteins participate in viral DNA replication and transcriptional regulation. We have solved the solution structure of the DNA-binding domain of the E2 protein from bovine papillomavirus (BPV-1). The structure calculation used 2222 distance and 158 dihedral angle restraints for the homodimer (202 residues in total), which were derived from homonuclear and heteronuclear multidimensional nuclear magnetic resonance (NMR) spectroscopic data. The root-mean-square deviation for structured regions of the monomer when superimposed to the average is 0.73 +/- 0.10 A for backbone atoms and 1.42 +/- 0.16 A for heavy atoms. The 101 residue construct used in this study (residues 310-410) is about 4.5 kcal/mol more stable than a minimal domain comprising the C-terminal 85 amino acid residues (residues 326-410). The structure of the core domain contained within BPV-1 E2 is similar to the corresponding regions of other papilloma viral E2 proteins. Here, however, the extra N-terminal 16 residues form a flap that covers a cavity at the dimer interface and play a role in DNA binding. Interactions between residues in the N-terminal extension and the core domain correlate with the greater stability of the longer form of the protein relative to the minimal domain.
GO:0003677
DNA binding
GO:0003700
transcription factor activity, sequence-specific DNA binding
GO:0005515
protein binding
GO:0000166
nucleotide binding
GO:0006355
regulation of transcription, DNA-templated
GO:0006275
regulation of DNA replication
GO:0039693
viral DNA genome replication
GO:0006351
transcription, DNA-templated
GO:0042025
host cell nucleus
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Other
E2 dimer
A
Regulatory protein E2
Bovine papillomavirus type 1
RRTTNDGFHLLKAGGSCFALISGTANQVKCYRFRVKKNHRHRYENCTTTWFTVADNGAERQGQAQILITFGSPSQRQDFLKHVPLPPGMNISGFTASLDF
100
P03122
311
410
24.4%
UniRef90_P03122
311
410
secondary structure
beta
327
333
secondary structure
helix
335
352
secondary structure
beta
355
356
secondary structure
beta
363
363
secondary structure
beta
370
370
secondary structure
beta
374
380
secondary structure
helix
383
387
secondary structure
helix
389
392
secondary structure
beta
401
408
pfam
PF00511.14
PPV_E2_C
328
405
B
Regulatory protein E2
Bovine papillomavirus type 1
RRTTNDGFHLLKAGGSCFALISGTANQVKCYRFRVKKNHRHRYENCTTTWFTVADNGAERQGQAQILITFGSPSQRQDFLKHVPLPPGMNISGFTASLDF
100
P03122
311
410
24.4%
UniRef90_P03122
311
410
secondary structure
beta
327
333
secondary structure
helix
335
345
secondary structure
helix
349
352
secondary structure
beta
355
356
secondary structure
beta
360
360
secondary structure
beta
363
363
secondary structure
beta
370
370
secondary structure
beta
374
379
secondary structure
helix
383
392
secondary structure
beta
401
408
pfam
PF00511.14
PPV_E2_C
328
405
The DNA binding domain of E2 was shown to exhibit a two-state concerted unfolding and dissociation in denaturation/renaturation experiments (PMID:8745409, PMID:8756330).
1jjh
2bop
MF6100001
Heat shock factor binding protein 1 (HSBP1)
3ci9
X-ray
1.80
homohexamer (dimer of trimers)
Homo sapiens
18767159
Liu X, Xu L, Liu Y, Tong X, Zhu G, Zhang XC, Li X, Rao Z
Crystal structure of the hexamer of human heat shock factor binding protein 1.
Proteins
2009
1
75
1-11
Heat shock response (HSR) is a ubiquitous cellular mechanism that copes with a variety of stresses. This response is mediated by a family of transcriptional activators, heat shock factors (HSFs), which are under tight regulation. HSF binding protein 1 (HSBP1) is a negative regulator of HSR and is reported to bind specifically with the active trimeric form of HSF1, thus inhibiting its activity. HSBP1 contains heptad-repeats in the primary sequence and was believed to stay in a trimer form in solution. We report the crystal structure of the trimerization domain of the M30I/L55P mutant of human HSBP1 at 1.8 A resolution. In this crystal form, the HSBP1 fragment of residues 6-53 forms a continuous, 11-turn long helix. The helix self-associates to form a parallel, symmetrical, triple coiled-coil helix bundle, which further assembles into a dimer of trimers in a head-to-head fashion. Solution study confirmed that the wild-type HSBP1 shares similar biophysical properties with the crystallized variant. Furthermore, we identified Ser31, which buried its polar side chain in the hydrophobic interior of the helix bundle, as a stability weak-spot. Substitution of this residue with Ile increases the melting temperature by 24 degrees C, implicating that this conserved serine residue is maintained at position 31 for functional purposes.
GO:0003714
transcription corepressor activity
GO:0005515
protein binding
GO:0035987
endodermal cell differentiation
GO:0000122
negative regulation of transcription from RNA polymerase II promoter
GO:0006936
muscle contraction
GO:1900034
regulation of cellular response to heat
GO:0005856
cytoskeleton
GO:0005654
nucleoplasm
Chains C and E were generated from chain A and chains D and F were generated from chain B using the biomatrices described in the original PDB file.
6
1
Coils and zippers
Coiled coil (hexameric)
A
Heat shock factor-binding protein 1
Homo sapiens
PKTVQDLTSVVQTLLQQMQDKFQTISDQIIGRIDDMSSRIDDLEKNIA
48
O75506
6
53
63.2%
UniRef90_O75506
6
53
secondary structure
helix
9
46
pfam
PF06825.9
HSBP1
10
60
B
Heat shock factor-binding protein 1
Homo sapiens
PKTVQDLTSVVQTLLQQMQDKFQTISDQIIGRIDDMSSRIDDLEKNIA
48
O75506
6
53
63.2%
UniRef90_O75506
6
53
secondary structure
helix
10
52
pfam
PF06825.9
HSBP1
10
60
C
Heat shock factor-binding protein 1
Homo sapiens
PKTVQDLTSVVQTLLQQMQDKFQTISDQIIGRIDDMSSRIDDLEKNIA
48
O75506
6
53
63.2%
UniRef90_O75506
6
53
secondary structure
helix
9
46
pfam
PF06825.9
HSBP1
10
60
D
Heat shock factor-binding protein 1
Homo sapiens
PKTVQDLTSVVQTLLQQMQDKFQTISDQIIGRIDDMSSRIDDLEKNIA
48
O75506
6
53
63.2%
UniRef90_O75506
6
53
secondary structure
helix
10
52
pfam
PF06825.9
HSBP1
10
60
E
Heat shock factor-binding protein 1
Homo sapiens
PKTVQDLTSVVQTLLQQMQDKFQTISDQIIGRIDDMSSRIDDLEKNIA
48
O75506
6
53
63.2%
UniRef90_O75506
6
53
secondary structure
helix
9
46
pfam
PF06825.9
HSBP1
10
60
F
Heat shock factor-binding protein 1
Homo sapiens
PKTVQDLTSVVQTLLQQMQDKFQTISDQIIGRIDDMSSRIDDLEKNIA
48
O75506
6
53
63.2%
UniRef90_O75506
6
53
secondary structure
helix
10
52
pfam
PF06825.9
HSBP1
10
60
The subunits in the structure are bound via coiled coil interactions (PMID:18767159). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
MF6120001
4-oxalocrotonate tautomerase
4x19
X-ray
1.94
homohexamer
Pseudomonas putida
25728471
Poddar H, Rahimi M, Geertsema EM, Thunnissen AM, Poelarends GJ
Evidence for the Formation of an Enamine Species during Aldol and Michael-type Addition Reactions Promiscuously Catalyzed by 4-Oxalocrotonate Tautomerase.
Chembiochem
2015
The enzyme 4-oxalocrotonate tautomerase (4-OT), which has a catalytic N-terminal proline residue (Pro1), can promiscuously catalyze various carbon-carbon bond-forming reactions, including aldol condensation of acetaldehyde with benzaldehyde to yield cinnamaldehyde, and Michael-type addition of acetaldehyde to a wide variety of nitroalkenes to yield valuable γ-nitroaldehydes. To gain insight into how 4-OT catalyzes these unnatural reactions, we carried out exchange studies in D2 O, and X-ray crystallography studies. The former established that H-D exchange within acetaldehyde is catalyzed by 4-OT and that the Pro1 residue is crucial for this activity. The latter showed that Pro1 of 4-OT had reacted with acetaldehyde to give an enamine species. These results provide evidence of the mechanism of the 4-OT-catalyzed aldol and Michael-type addition reactions in which acetaldehyde is activated for nucleophilic addition by Pro1-dependent formation of an enamine intermediate.
GO:0016853
isomerase activity
GO:0042184
xylene catabolic process
GO:0042203
toluene catabolic process
Chains G, H, I, J, K, L, M, N, O, P, Q, R, S, T, U, V, W, X, Y, Z, a, b, c and d were removed as chains A, B, C, D, E and F represent the biologically active hexamer.
6
1
Homooligomeric enzymes
Homohexameric enzymes
A
2-hydroxymuconate tautomerase
Pseudomonas putida
PIAQIHILEGRSDEQKETLIREVSEAISRSLDAPLTSVRVIITEMAKGHFGIGGELASKVRR
62
Q01468
2
63
98.4%
UniRef90_Q01468
2
63
secondary structure
beta
3
9
secondary structure
helix
14
32
secondary structure
helix
36
38
secondary structure
beta
40
46
secondary structure
helix
48
50
secondary structure
beta
51
53
secondary structure
beta
56
57
pfam
PF01361.18
Tautomerase
2
60
B
2-hydroxymuconate tautomerase
Pseudomonas putida
PIAQIHILEGRSDEQKETLIREVSEAISRSLDAPLTSVRVIITEMAKGHFGIGGELASKVRR
62
Q01468
2
63
98.4%
UniRef90_Q01468
2
63
secondary structure
beta
3
9
secondary structure
helix
14
32
secondary structure
helix
36
38
secondary structure
beta
40
46
secondary structure
helix
48
50
secondary structure
beta
51
53
secondary structure
beta
56
56
pfam
PF01361.18
Tautomerase
2
60
C
2-hydroxymuconate tautomerase
Pseudomonas putida
PIAQIHILEGRSDEQKETLIREVSEAISRSLDAPLTSVRVIITEMAKGHFGIGGELASKVRR
62
Q01468
2
63
98.4%
UniRef90_Q01468
2
63
secondary structure
beta
3
9
secondary structure
helix
14
32
secondary structure
helix
36
38
secondary structure
beta
40
46
secondary structure
helix
48
50
secondary structure
beta
51
53
secondary structure
beta
56
57
pfam
PF01361.18
Tautomerase
2
60
D
2-hydroxymuconate tautomerase
Pseudomonas putida
PIAQIHILEGRSDEQKETLIREVSEAISRSLDAPLTSVRVIITEMAKGHFGIGGELASKVRR
62
Q01468
2
63
98.4%
UniRef90_Q01468
2
63
secondary structure
beta
3
9
secondary structure
helix
14
32
secondary structure
helix
36
38
secondary structure
beta
40
46
secondary structure
helix
48
50
secondary structure
beta
51
53
secondary structure
beta
56
57
pfam
PF01361.18
Tautomerase
2
60
E
2-hydroxymuconate tautomerase
Pseudomonas putida
PIAQIHILEGRSDEQKETLIREVSEAISRSLDAPLTSVRVIITEMAKGHFGIGGELASKVRR
62
Q01468
2
63
98.4%
UniRef90_Q01468
2
63
secondary structure
beta
3
9
secondary structure
helix
14
32
secondary structure
helix
36
38
secondary structure
beta
40
46
secondary structure
helix
48
50
secondary structure
beta
51
53
secondary structure
beta
56
57
pfam
PF01361.18
Tautomerase
2
60
F
2-hydroxymuconate tautomerase
Pseudomonas putida
PIAQIHILEGRSDEQKETLIREVSEAISRSLDAPLTSVRVIITEMAKGHFGIGGELASKVRR
62
Q01468
2
63
98.4%
UniRef90_Q01468
2
63
secondary structure
beta
3
9
secondary structure
helix
14
32
secondary structure
helix
36
38
secondary structure
beta
40
46
secondary structure
helix
48
50
secondary structure
beta
51
53
secondary structure
beta
56
57
pfam
PF01361.18
Tautomerase
2
60
4-oxalocrotonate tautomerase hexamer from Pseudomonas putida was shown by DSC to follow a two-state folding with the hexameric, dimeric and secondary structure all melting at the same temperature (PMID:20465238).
1bjp
2fm7
4ota
4otb
4otc
4x1c
5cln
5clo
MF2120019
Escherichia coli met repressor (MetJ)
1cmb
X-ray
1.80
homodimer
Escherichia coli
2677753
Rafferty JB, Somers WS, Saint-Girons I, Phillips SE
Three-dimensional crystal structures of Escherichia coli met repressor with and without corepressor.
Nature
1989
6244
341
705-10
The three-dimensional crystal structure of met repressor, in the presence or absence of bound corepressor (S-adenosylmethionine), shows a dimer of intertwined monomers, which do not have the helix-turn-helix motif characteristic of other bacterial repressor and activator structures. We propose that the interaction of met repressor with DNA occurs through either a pair of symmetry-related alpha-helices or a pair of beta-strands, and suggest a model for binding of several dimers to met operator regions.
GO:0003677
DNA binding
GO:0003700
transcription factor activity, sequence-specific DNA binding
GO:0006351
transcription, DNA-templated
GO:0045892
negative regulation of transcription, DNA-templated
GO:0009086
methionine biosynthetic process
GO:0005829
cytosol
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Other
Other
A
Met repressor
Escherichia coli
AEWSGEYISPYAEHGKKSEQVKKITVSIPLKVLKILTDERTRRQVNNLRHATNSELLCEAFLHAFTGQPLPDDADLRKERSDEIPEAAKEIMREMGINPETWEY
104
P0A8U6
2
105
99%
UniRef90_A7ZUF7
2
105
secondary structure
beta
14
15
secondary structure
beta
18
19
secondary structure
beta
22
30
secondary structure
helix
31
47
secondary structure
beta
49
49
secondary structure
helix
54
67
secondary structure
helix
74
77
secondary structure
beta
78
78
secondary structure
helix
87
95
pfam
PF01340.17
MetJ
3
99
B
Met repressor
Escherichia coli
AEWSGEYISPYAEHGKKSEQVKKITVSIPLKVLKILTDERTRRQVNNLRHATNSELLCEAFLHAFTGQPLPDDADLRKERSDEIPEAAKEIMREMGINPETWEY
104
P0A8U6
2
105
99%
UniRef90_A7ZUF7
2
105
secondary structure
beta
22
30
secondary structure
helix
31
46
secondary structure
helix
54
67
secondary structure
beta
80
80
secondary structure
beta
83
83
secondary structure
helix
87
95
pfam
PF01340.17
MetJ
3
99
MetJ was shown by differential scanning calorimetry to follow a two-state folding and dimerization (PMID:1390748).
1cma
1cmc
1mj2
1mjk
1mjl
1mjm
1mjo
1mjp
1mjq
MF2110010
Nerve growth factor (NGF)
1bet
X-ray
2.30
homodimer
Mus musculus
1956407
McDonald NQ, Lapatto R, Murray-Rust J, Gunning J, Wlodawer A, Blundell TL
New protein fold revealed by a 2.3-A resolution crystal structure of nerve growth factor.
Nature
1991
6352
354
411-4
Nerve growth factor (NGF) is a member of an expanding family of neurotrophic factors (including brain-derived neurotrophic factor and the neurotrophins) that control the development and survival of certain neuronal populations both in the peripheral and in the central nervous systems. Its biological effects are mediated by a high-affinity ligand-receptor interaction and a tyrosine kinase signalling pathway. A potential use for NGF and its relatives in the treatment of neurological disorders such as Alzheimer's disease and Parkinson's disease requires an understanding of the structure-function relationships of NGF. NGF is a dimeric molecule, with 118 amino acids per protomer. We report the crystal structure of the murine NGF dimer at 2.3-A resolution, which reveals a novel protomer structure consisting of three antiparallel pairs of beta strands, together forming a flat surface. Two subunits associate through this surface, thus burying a total of 2,332 A. Four loop regions, which contain many of the variable residues observed between different NGF-related molecules, may determine the different receptor specificities. A clustering of positively charged side chains may provide a complementary interaction with the acidic low-affinity NGF receptor. The structure provides a model for rational design of analogues of NGF and its relatives and for testing the NGF-receptor recognition determinants critical for signal transduction.
GO:0030297
transmembrane receptor protein tyrosine kinase activator activity
GO:0005057
receptor signaling protein activity
GO:0008191
metalloendopeptidase inhibitor activity
GO:0005163
nerve growth factor receptor binding
GO:0008083
growth factor activity
GO:0007422
peripheral nervous system development
GO:0010951
negative regulation of endopeptidase activity
GO:0048672
positive regulation of collateral sprouting
GO:0048812
neuron projection morphogenesis
GO:0045773
positive regulation of axon extension
GO:0046928
regulation of neurotransmitter secretion
GO:0007171
activation of transmembrane receptor protein tyrosine kinase activity
GO:0097192
extrinsic apoptotic signaling pathway in absence of ligand
GO:0008625
extrinsic apoptotic signaling pathway via death domain receptors
GO:0046579
positive regulation of Ras protein signal transduction
GO:0048015
phosphatidylinositol-mediated signaling
GO:0038180
nerve growth factor signaling pathway
GO:0014042
positive regulation of neuron maturation
GO:0031954
positive regulation of protein autophosphorylation
GO:0019233
sensory perception of pain
GO:0043065
positive regulation of apoptotic process
GO:0007623
circadian rhythm
GO:0031398
positive regulation of protein ubiquitination
GO:0032455
nerve growth factor processing
GO:0051402
neuron apoptotic process
GO:0051279
regulation of release of sequestered calcium ion into cytosol
GO:0043524
negative regulation of neuron apoptotic process
GO:0051091
positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051388
positive regulation of neurotrophin TRK receptor signaling pathway
GO:0005788
endoplasmic reticulum lumen
GO:0005576
extracellular region
GO:0016023
cytoplasmic, membrane-bounded vesicle
Chain B was generated from chain A using the biomatrices described in the original PDB file.
2
1
NGF-like proteins
Homodimeric NGF-like proteins
A
Beta-nerve growth factor
Mus musculus
GEFSVCDSVSVWVGDKTTATDIKGKEVTVLAEVNINNSVFRQYFFETKCRASNPVESGCRGIDSKHWNSYCTTTHTFVKALTTDEKQAAWRFIRIDTACVCVLSRKA
107
P01139
131
237
44.4%
UniRef90_P01139
131
237
secondary structure
beta
133
134
secondary structure
beta
138
143
secondary structure
beta
148
151
secondary structure
beta
156
159
secondary structure
beta
162
165
secondary structure
beta
168
171
secondary structure
beta
174
179
secondary structure
beta
185
185
secondary structure
beta
188
188
secondary structure
beta
192
192
secondary structure
beta
197
213
secondary structure
beta
218
235
pfam
PF00243.15
NGF
128
238
B
Beta-nerve growth factor
Mus musculus
GEFSVCDSVSVWVGDKTTATDIKGKEVTVLAEVNINNSVFRQYFFETKCRASNPVESGCRGIDSKHWNSYCTTTHTFVKALTTDEKQAAWRFIRIDTACVCVLSRKA
107
P01139
131
237
44.4%
UniRef90_P01139
131
237
secondary structure
beta
133
134
secondary structure
beta
138
143
secondary structure
beta
148
151
secondary structure
beta
156
159
secondary structure
beta
162
165
secondary structure
beta
168
171
secondary structure
beta
174
179
secondary structure
beta
185
185
secondary structure
beta
188
188
secondary structure
beta
192
192
secondary structure
beta
197
213
secondary structure
beta
218
235
pfam
PF00243.15
NGF
128
238
Various dimeric members of neurotrophic factors (including human/mouse nerve growth factor, human brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4/5 (NT-4/5)) have been shown to fold and dimerize at the same time via a two-state process (PMID:8161524). While the members of this family show a significant variance in sequence, they adopt a highly similar structure upon binding and behave almost identically in unfolding/refolding experiments. Thus the two-state folding/binding nature seems to be a hallmark of NGF and closely related proteins.
1btg
4eax
1sgf
4xpj
MF2100007
Neurotrophin 3 homodimer
1b8k
X-ray
2.15
homodimer
Homo sapiens
10631974
Robinson RC, Radziejewski C, Spraggon G, Greenwald J, Kostura MR, Burtnick LD, Stuart DI, Choe S, Jones EY
The structures of the neurotrophin 4 homodimer and the brain-derived neurotrophic factor/neurotrophin 4 heterodimer reveal a common Trk-binding site.
Protein Sci.
1999
12
8
2589-97
The neurotrophins are growth factors that are involved in the development and survival of neurons. Neurotrophin release by a target tissue results in neuron growth along the neurotrophin concentration gradient, culminating in the eventual innervation of the target tissue. These activities are mediated through trk cell surface receptors. We have determined the structures of the heterodimer formed between brain-derived neurotrophic factor (BDNF) and neurotrophin 4 (NT4), as well as the structure of homodimer of NT4. We also present the structure of the Neurotrophin 3 homodimer, which is refined to higher resolution than previously published. These structures provide the first views of the architecture of the NT4 protomer. Comparison of the surface of a model of the BDNF homodimer with the structures of the neurotrophin homodimers reveals common features that may be important in the binding between the neurotrophins and their receptors. In particular, there exists an analogous region on the surface of each neurotrophin that is likely to be involved in trk receptor binding. Variations in sequence on the periphery of this common region serve to confer trk receptor specificity.
GO:0005166
neurotrophin p75 receptor binding
GO:0008083
growth factor activity
GO:0042056
chemoattractant activity
GO:0048406
nerve growth factor binding
GO:0045664
regulation of neuron differentiation
GO:0000187
activation of MAPK activity
GO:0050731
positive regulation of peptidyl-tyrosine phosphorylation
GO:0050930
induction of positive chemotaxis
GO:0090630
activation of GTPase activity
GO:0050804
modulation of synaptic transmission
GO:0033138
positive regulation of peptidyl-serine phosphorylation
GO:0050918
positive chemotaxis
GO:0007169
transmembrane receptor protein tyrosine kinase signaling pathway
GO:0048812
neuron projection morphogenesis
GO:0002092
positive regulation of receptor internalization
GO:0008284
positive regulation of cell proliferation
GO:0045687
positive regulation of glial cell differentiation
GO:0042552
myelination
GO:0007267
cell-cell signaling
GO:2000251
positive regulation of actin cytoskeleton reorganization
GO:0043524
negative regulation of neuron apoptotic process
GO:0032148
activation of protein kinase B activity
GO:0030335
positive regulation of cell migration
GO:0050732
negative regulation of peptidyl-tyrosine phosphorylation
GO:0016023
cytoplasmic, membrane-bounded vesicle
GO:0005576
extracellular region
Chain B was generated from chain A using the biomatrices described in the original PDB file.
2
1
NGF-like proteins
Homodimeric NGF-like proteins
A
Neurotrophin-3
Homo sapiens
YAEHKSHRGEYSVCDSESLWVTDKSSAIDIRGHQVTVLGEIKTGNSPVKQYFYETRCKEARPVKNGCRGIDDKHWNSQCKTSQTYVRALTSENNKLVGWRWIRIDTSCVCALSRKIGRT
119
P20783
139
257
46.3%
UniRef90_P20783
139
257
secondary structure
beta
150
150
secondary structure
beta
154
159
secondary structure
beta
164
167
secondary structure
beta
172
175
secondary structure
beta
178
178
secondary structure
beta
187
187
secondary structure
beta
190
195
secondary structure
beta
208
208
secondary structure
beta
216
229
secondary structure
beta
236
249
pfam
PF00243.15
NGF
144
255
B
Neurotrophin-3
Homo sapiens
YAEHKSHRGEYSVCDSESLWVTDKSSAIDIRGHQVTVLGEIKTGNSPVKQYFYETRCKEARPVKNGCRGIDDKHWNSQCKTSQTYVRALTSENNKLVGWRWIRIDTSCVCALSRKIGRT
119
P20783
139
257
46.3%
UniRef90_P20783
139
257
secondary structure
beta
150
150
secondary structure
beta
154
159
secondary structure
beta
164
167
secondary structure
beta
172
175
secondary structure
beta
178
178
secondary structure
beta
187
187
secondary structure
beta
190
195
secondary structure
beta
208
208
secondary structure
beta
216
229
secondary structure
beta
236
249
pfam
PF00243.15
NGF
144
255
Various dimeric members of neurotrophic factors (including human/mouse nerve growth factor, human brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4/5 (NT-4/5)) have been shown to fold and dimerize at the same time via a two-state process (PMID:8161524). While the members of this family show a significant variance in sequence, they adopt a highly similar structure upon binding and behave almost identically in unfolding/refolding experiments. Thus the two-state folding/binding nature seems to be a hallmark of NGF and closely related proteins.
1nt3
3buk
MF2100008
Neurotrophin 4 homodimer
1b98
X-ray
2.75
homodimer
Homo sapiens
10631974
Robinson RC, Radziejewski C, Spraggon G, Greenwald J, Kostura MR, Burtnick LD, Stuart DI, Choe S, Jones EY
The structures of the neurotrophin 4 homodimer and the brain-derived neurotrophic factor/neurotrophin 4 heterodimer reveal a common Trk-binding site.
Protein Sci.
1999
12
8
2589-97
The neurotrophins are growth factors that are involved in the development and survival of neurons. Neurotrophin release by a target tissue results in neuron growth along the neurotrophin concentration gradient, culminating in the eventual innervation of the target tissue. These activities are mediated through trk cell surface receptors. We have determined the structures of the heterodimer formed between brain-derived neurotrophic factor (BDNF) and neurotrophin 4 (NT4), as well as the structure of homodimer of NT4. We also present the structure of the Neurotrophin 3 homodimer, which is refined to higher resolution than previously published. These structures provide the first views of the architecture of the NT4 protomer. Comparison of the surface of a model of the BDNF homodimer with the structures of the neurotrophin homodimers reveals common features that may be important in the binding between the neurotrophins and their receptors. In particular, there exists an analogous region on the surface of each neurotrophin that is likely to be involved in trk receptor binding. Variations in sequence on the periphery of this common region serve to confer trk receptor specificity.
GO:0008083
growth factor activity
GO:0005166
neurotrophin p75 receptor binding
GO:0007267
cell-cell signaling
GO:0043524
negative regulation of neuron apoptotic process
GO:0008344
adult locomotory behavior
GO:0042490
mechanoreceptor differentiation
GO:0008052
sensory organ boundary specification
GO:0007402
ganglion mother cell fate determination
GO:0007616
long-term memory
GO:0008544
epidermis development
GO:0061193
taste bud development
GO:0045664
regulation of neuron differentiation
GO:0048812
neuron projection morphogenesis
GO:0060384
innervation
GO:0007169
transmembrane receptor protein tyrosine kinase signaling pathway
GO:0016023
cytoplasmic, membrane-bounded vesicle
GO:0005576
extracellular region
GO:0005788
endoplasmic reticulum lumen
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
NGF-like proteins
Homodimeric NGF-like proteins
A
Neurotrophin-4
Homo sapiens
GVSETAPASRRGELAVCDAVSGWVTDRRTAVDLRGREVEVLGEVPAAGGSPLRQYFFETRCKADNAEEGGPGAGGGGCRGVDRRHWVSECKAKQSYVRALTADAQGRVGWRWIRIDTACVCTLLSRTGRA
130
P34130
81
210
61.9%
UniRef90_P34130
81
210
secondary structure
beta
95
95
secondary structure
beta
99
104
secondary structure
beta
109
112
secondary structure
beta
117
120
secondary structure
beta
136
141
secondary structure
beta
161
161
secondary structure
beta
168
181
secondary structure
beta
189
203
pfam
PF00243.15
NGF
89
208
M
Neurotrophin-4
Homo sapiens
GVSETAPASRRGELAVCDAVSGWVTDRRTAVDLRGREVEVLGEVPAAGGSPLRQYFFETRCKADNAEEGGPGAGGGGCRGVDRRHWVSECKAKQSYVRALTADAQGRVGWRWIRIDTACVCTLLSRTGRA
130
P34130
81
210
61.9%
UniRef90_P34130
81
210
secondary structure
beta
94
95
secondary structure
beta
99
104
secondary structure
beta
109
112
secondary structure
beta
117
120
secondary structure
beta
123
124
secondary structure
beta
132
133
secondary structure
beta
136
141
secondary structure
beta
161
161
secondary structure
beta
167
182
secondary structure
beta
188
205
pfam
PF00243.15
NGF
89
208
Various dimeric members of neurotrophic factors (including human/mouse nerve growth factor, human brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4/5 (NT-4/5)) have been shown to fold and dimerize at the same time via a two-state process (PMID:8161524). While the members of this family show a significant variance in sequence, they adopt a highly similar structure upon binding and behave almost identically in unfolding/refolding experiments. Thus the two-state folding/binding nature seems to be a hallmark of NGF and closely related proteins.
1hcf
MF2200009
Brain-derived neurotrophic factor/neurotrophin 3 heterodimer
1bnd
X-ray
2.30
heterodimer
Homo sapiens
7703225
Robinson RC, Radziejewski C, Stuart DI, Jones EY
Structure of the brain-derived neurotrophic factor/neurotrophin 3 heterodimer.
Biochemistry
1995
13
34
4139-46
The development and sustenance of specific neuronal populations in the peripheral and central nervous systems are controlled through the binding of neurotrophic factors to high-affinity cell surface receptors. The neurotrophins (nerve growth factor, NGF; brain-derived neurotrophic factor, BDNF; neurotrophin 3, NT3; and neurotrophin 4, NT4) are dimeric molecules which share approximately 50% sequence identity. The crystal structure of the murine NGF homodimer [McDonald et al. (1991) Nature 354, 411-414] indicated that the dimer interface corresponds to regions of high sequence conservation throughout the neurotrophin family. This potential compatibility was duly exploited for the production in vitro of noncovalent heterodimers between the different neurotrophins [Radziejewski, C., & Robinson, R.C. (1993) Biochemistry 32, 13350-13356; Jungbluth et al. (1994) Eur. J. Biochem. 221, 677-685]. Here, we report the X-ray structure at 2.3 A resolution of one such heterodimer, between human BDNF, and human NT3. The NGF, BDNF, and NT3 protomers share the same topology and are structurally equivalent in regions which contribute to the dimer interface in line with the propensity of the neurotrophins to form heterodimers. Analysis of the structure of regions of the BDNF/NT3 heterodimer involved in receptor specificity led us to conclude that heterodimer binding to p75 involves distant binding sites separately located on each protomer of the heterodimer. In contrast, heterodimer interactions with the trk receptors probably utilize hybrid binding sites comprised of residues contributed by both protomers in the heterodimer. The existence of such hybrid binding sites for the trk receptor provides an explanation for the lower activity of the BDNF/NT3 heterodimer in comparison to the homodimers.(ABSTRACT TRUNCATED AT 250 WORDS)
GO:0008083
growth factor activity
GO:0007267
cell-cell signaling
GO:0043524
negative regulation of neuron apoptotic process
GO:0007399
nervous system development
GO:0016023
cytoplasmic, membrane-bounded vesicle
GO:0005576
extracellular region
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
2
NGF-like proteins
Heterodimeric NGF-like proteins
A
Brain-derived neurotrophic factor
Homo sapiens
HSDPARRGQLSVCDSISEWVTAADKKTAVDMSGGTVTVLEKVPVSKGQLKQYFYETKCNPMGYTKEGCRGIDKRHWNSQCRTTQSYVRALTMDSKKRIGWRFIRIDTSCVCTLTIKRGR
119
P23560
129
247
48.2%
UniRef90_P23560
129
247
secondary structure
beta
138
139
secondary structure
beta
143
149
secondary structure
helix
150
153
secondary structure
beta
155
158
secondary structure
beta
163
166
secondary structure
beta
169
171
secondary structure
beta
176
178
secondary structure
beta
180
186
secondary structure
helix
191
193
secondary structure
beta
199
199
secondary structure
beta
204
220
secondary structure
beta
226
243
pfam
PF00243.15
NGF
133
246
B
Neurotrophin-3
Homo sapiens
YAEHKSHRGEVSVCDSESLWVTDKSSAIDIRGHQVTVLGEIKTQNSPVKQYFYETRCKEARPVKNGCRGIDDKHWNSQCKTSQTYVRALTSENNKLVGWRWIRIDTSCVCALSRKIGRT
119
P20783
139
257
46.3%
UniRef90_P20783
139
257
secondary structure
beta
148
150
secondary structure
beta
154
159
secondary structure
beta
164
167
secondary structure
beta
172
175
secondary structure
beta
178
179
secondary structure
beta
186
187
secondary structure
beta
190
195
secondary structure
beta
208
208
secondary structure
beta
214
230
secondary structure
beta
233
251
pfam
PF00243.15
NGF
144
255
Various dimeric members of neurotrophic factors (including human/mouse nerve growth factor, human brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4/5 (NT-4/5)) have been shown to fold and dimerize at the same time via a two-state process (PMID:8161524). While the members of this family show a significant variance in sequence, they adopt a highly similar structure upon binding and behave almost identically in unfolding/refolding experiments. Thus the two-state folding/binding nature seems to be a hallmark of NGF and closely related proteins.
MF2201009
Brain-derived neurotrophic factor/neurotrophin 4 heterodimer
1b8m
X-ray
2.75
heterodimer
Sus scrofa / Homo sapiens
10631974
Robinson RC, Radziejewski C, Spraggon G, Greenwald J, Kostura MR, Burtnick LD, Stuart DI, Choe S, Jones EY
The structures of the neurotrophin 4 homodimer and the brain-derived neurotrophic factor/neurotrophin 4 heterodimer reveal a common Trk-binding site.
Protein Sci.
1999
12
8
2589-97
The neurotrophins are growth factors that are involved in the development and survival of neurons. Neurotrophin release by a target tissue results in neuron growth along the neurotrophin concentration gradient, culminating in the eventual innervation of the target tissue. These activities are mediated through trk cell surface receptors. We have determined the structures of the heterodimer formed between brain-derived neurotrophic factor (BDNF) and neurotrophin 4 (NT4), as well as the structure of homodimer of NT4. We also present the structure of the Neurotrophin 3 homodimer, which is refined to higher resolution than previously published. These structures provide the first views of the architecture of the NT4 protomer. Comparison of the surface of a model of the BDNF homodimer with the structures of the neurotrophin homodimers reveals common features that may be important in the binding between the neurotrophins and their receptors. In particular, there exists an analogous region on the surface of each neurotrophin that is likely to be involved in trk receptor binding. Variations in sequence on the periphery of this common region serve to confer trk receptor specificity.
GO:0008083
growth factor activity
GO:0007169
transmembrane receptor protein tyrosine kinase signaling pathway
GO:0048812
neuron projection morphogenesis
GO:0045664
regulation of neuron differentiation
GO:0007267
cell-cell signaling
GO:0043524
negative regulation of neuron apoptotic process
GO:0016023
cytoplasmic, membrane-bounded vesicle
GO:0005576
extracellular region
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
2
NGF-like proteins
Heterodimeric NGF-like proteins
A
Brain-derived neurotrophic factor
Sus scrofa
HSDPARRGELSVCDSISEWVTAADKKTAVDMSGGTVTVLEKVPVSKGQLKQYFYETKCNPMGYTKEGCRGIDKRHWNSQCRTTQSYVRALTMDSKKRIGWRFIRIDTSCVCTLTIKRGR
119
P14082
134
252
47.2%
UniRef90_P23560-3
144
262
secondary structure
beta
144
144
secondary structure
beta
148
154
secondary structure
helix
155
158
secondary structure
beta
160
163
secondary structure
beta
168
171
secondary structure
beta
174
177
secondary structure
beta
180
183
secondary structure
beta
185
191
secondary structure
beta
204
204
secondary structure
beta
210
225
secondary structure
beta
231
247
pfam
PF00243.15
NGF
138
251
B
Neurotrophin-4
Homo sapiens
GVSETAPASRRGELAVCDAVSGWVTDRRTAVDLRGREVEVLGEVPAAGGSPLRQYFFETRCKADNAEEGGPGAGGGGCRGVDRRHWVSECKAKQSYVRALTADAQGRVGWRWIRIDTACVCTLLSRTGRA
130
P34130
81
210
61.9%
UniRef90_P34130
81
210
secondary structure
beta
93
95
secondary structure
beta
99
104
secondary structure
beta
109
112
secondary structure
beta
117
120
secondary structure
beta
123
124
secondary structure
beta
132
133
secondary structure
beta
136
141
secondary structure
beta
161
161
secondary structure
beta
167
182
secondary structure
beta
188
205
pfam
PF00243.15
NGF
89
208
Various dimeric members of neurotrophic factors (including human/mouse nerve growth factor, human brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4/5 (NT-4/5)) have been shown to fold and dimerize at the same time via a two-state process (PMID:8161524). While the members of this family show a significant variance in sequence, they adopt a highly similar structure upon binding and behave almost identically in unfolding/refolding experiments. Thus the two-state folding/binding nature seems to be a hallmark of NGF and closely related proteins.
MF2110011
Ovulation-inducing factor (OIF) from llama seminal plasma
4efv
X-ray
2.32
homodimer
Saimiri boliviensis boliviensis
22908303
Ratto MH, Leduc YA, Valderrama XP, van Straaten KE, Delbaere LT, Pierson RA, Adams GP
The nerve of ovulation-inducing factor in semen.
Proc. Natl. Acad. Sci. U.S.A.
2012
37
109
15042-7
A component in seminal fluid elicits an ovulatory response and has been discovered in every species examined thus far. The existence of an ovulation-inducing factor (OIF) in seminal plasma has broad implications and evokes questions about identity, tissue sources, mechanism of action, role among species, and clinical relevance in infertility. Most of these questions remain unanswered. The goal of this study was to determine the identity of OIF in support of the hypothesis that it is a single distinct and widely conserved entity. Seminal plasma from llamas and bulls was used as representative of induced and spontaneous ovulators, respectively. A fraction isolated from llama seminal plasma by column chromatography was identified as OIF by eliciting luteinizing hormone (LH) release and ovulation in llamas. MALDI-TOF revealed a molecular mass of 13,221 Da, and 12-23 aa sequences of OIF had homology with human, porcine, bovine, and murine sequences of β nerve growth factor (β-NGF). X-ray diffraction data were used to solve the full sequence and structure of OIF as β-NGF. Neurite development and up-regulation of trkA in phaeochromocytoma (PC(12)) cells in vitro confirmed NGF-like properties of OIF. Western blot analysis of llama and bull seminal plasma confirmed immunorecognition of OIF using polyclonal mouse anti-NGF, and administration of β-NGF from mouse submandibular glands induced ovulation in llamas. We conclude that OIF in seminal plasma is β-NGF and that it is highly conserved. An endocrine route of action of NGF elucidates a previously unknown pathway for the direct influence of the male on the hypothalamo-pituitary-gonadal axis of the inseminated female.
GO:0008083
growth factor activity
GO:0008191
metalloendopeptidase inhibitor activity
GO:0010951
negative regulation of endopeptidase activity
GO:0005576
extracellular region
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
NGF-like proteins
Homodimeric NGF-like proteins
A
Beta-nerve growth factor
Saimiri boliviensis boliviensis
APSHPIFHRGEFSVCDSVSVWVADKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCRDPNPVASGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSKKAS
117
Q5ISB0
124
238
47.7%
UniRef90_P13600
124
236
secondary structure
beta
133
134
secondary structure
beta
138
143
secondary structure
beta
148
151
secondary structure
beta
156
159
secondary structure
beta
162
164
secondary structure
beta
169
171
secondary structure
beta
174
179
secondary structure
beta
192
192
secondary structure
helix
194
196
secondary structure
beta
197
213
secondary structure
beta
218
235
pfam
PF00243.15
NGF
128
238
B
Beta-nerve growth factor
Saimiri boliviensis boliviensis
APSHPIFHRGEFSVCDSVSVWVADKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCRDPNPVASGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSKKAS
117
Q5ISB0
124
238
47.7%
UniRef90_P13600
124
236
secondary structure
beta
133
134
secondary structure
beta
138
143
secondary structure
beta
148
151
secondary structure
beta
156
159
secondary structure
beta
162
165
secondary structure
beta
168
171
secondary structure
beta
174
179
secondary structure
beta
192
192
secondary structure
beta
197
213
secondary structure
beta
218
235
pfam
PF00243.15
NGF
128
238
Various dimeric members of neurotrophic factors (including human/mouse nerve growth factor, human brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4/5 (NT-4/5)) have been shown to fold and dimerize at the same time via a two-state process (PMID:8161524). While the members of this family show a significant variance in sequence, they adopt a highly similar structure upon binding and behave almost identically in unfolding/refolding experiments. Thus the two-state folding/binding nature seems to be a hallmark of NGF and closely related proteins. While OIF plays a different biological role than NGF, they share a 97% sequence identity and have virtually identical structures.
MF2110012
Dimerization domain of HNF-1alpha
1jb6
X-ray
1.70
homodimer
Mus musculus
11439029
Narayana N, Hua Q, Weiss MA
The dimerization domain of HNF-1alpha: structure and plasticity of an intertwined four-helix bundle with application to diabetes mellitus.
J. Mol. Biol.
2001
3
310
635-58
Maturity-onset diabetes mellitus of the young (MODY) is a human genetic syndrome most commonly due to mutations in hepatocyte nuclear factor-1alpha (HNF-1alpha). Here, we describe the crystal structure of the HNF-1alpha dimerization domain at 1.7 A resolution and assess its structural plasticity. The crystal's low solvent content (23%, v/v) leads to tight packing of peptides in the lattice. Two independent dimers, similar in structure, are formed in the unit cell by a 2-fold crystallographic symmetry axis. The dimers define a novel intertwined four-helix bundle (4HB). Each protomer contains two alpha-helices separated by a sharp non-canonical turn. Dimer-related alpha-helices form anti-parallel coiled-coils, including an N-terminal "mini-zipper" complementary in structure, symmetry and surface characteristics to transcriptional coactivator dimerization cofactor of HNF-1 (DCoH). A confluence of ten leucine side-chains (five per protomer) forms a hydrophobic core. Isotope-assisted NMR studies demonstrate that a similar intertwined dimer exists in solution. Comparison of structures obtained in multiple independent crystal forms indicates that the mini-zipper is a stable structural element, whereas the C-terminal alpha-helix can adopt a broad range of orientations. Segmental alignment of the mini-zipper (mean pairwise root-mean-square difference (rmsd) in C(alpha) coordinates of 0.29 A) is associated with a 2.1 A mean C(alpha) rmsd displacement of the C-terminal coiled-coil. The greatest C-terminal structural variation (4.1 A C(alpha) rmsd displacement) is observed in the DCoH-bound peptide. Diabetes-associated mutations perturb distinct structural features of the HNF-1alpha domain. One mutation (L12H) destabilizes the domain but preserves structural specificity. Adjoining H12 side-chains in a native-like dimer are predicted to alter the functional surface of the mini-zipper involved in DCoH recognition. The other mutation (G20R), by contrast, leads to a dimeric molten globule, as indicated by its 1H-NMR features and fluorescent binding of 1-anilino-8-naphthalene sulfonate. We propose that a glycine-specific turn configuration enables specific interactions between the mini-zipper and the C-terminal coiled-coil.
GO:0001221
transcription cofactor binding
GO:0001077
transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0046982
protein heterodimerization activity
GO:0042803
protein homodimerization activity
GO:0000978
RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0042593
glucose homeostasis
GO:0006699
bile acid biosynthetic process
GO:0030073
insulin secretion
GO:0048341
paraxial mesoderm formation
GO:0060261
positive regulation of transcription initiation from RNA polymerase II promoter
GO:0015908
fatty acid transport
GO:0015721
bile acid and bile salt transport
GO:0035623
renal glucose absorption
GO:0009749
response to glucose
GO:0030326
embryonic limb morphogenesis
GO:0046323
glucose import
GO:0001824
blastocyst development
GO:0031018
endocrine pancreas development
GO:0006633
fatty acid biosynthetic process
GO:0001889
liver development
GO:0000122
negative regulation of transcription from RNA polymerase II promoter
GO:0006366
transcription from RNA polymerase II promoter
GO:0008203
cholesterol metabolic process
GO:0006338
chromatin remodeling
GO:0050796
regulation of insulin secretion
GO:0043691
reverse cholesterol transport
GO:0016573
histone acetylation
GO:0006783
heme biosynthetic process
GO:0001890
placenta development
GO:0006979
response to oxidative stress
GO:0045453
bone resorption
GO:0030111
regulation of Wnt signaling pathway
GO:0060395
SMAD protein signal transduction
GO:0005667
transcription factor complex
GO:0001750
photoreceptor outer segment
GO:0005737
cytoplasm
GO:0005654
nucleoplasm
GO:0045120
pronucleus
Chain C was generated from chain A using the biomatrix described in the original PDB file. Chain B was removed as chains A and C represent the biologically active dimer.
2
1
Coils and zippers
Coiled coil (dimeric, forming a 4-helix bundle)
A
Hepatocyte nuclear factor 1-alpha
Mus musculus
VSKLSQLQTELMAALLESGLSKEALIQALGEW
32
P22361
1
33
5.3%
UniRef90_P22361
2
32
secondary structure
helix
5
12
secondary structure
helix
14
20
secondary structure
helix
25
32
pfam
PF04814.10
HNF-1_N
8
168
C
Hepatocyte nuclear factor 1-alpha
Mus musculus
VSKLSQLQTELMAALLESGLSKEALIQALGEW
32
P22361
1
33
5.3%
UniRef90_P22361
2
32
secondary structure
helix
5
12
secondary structure
helix
14
20
secondary structure
helix
25
32
pfam
PF04814.10
HNF-1_N
8
168
HNF dimer The thermal and chemical equilibrium unfolding of a 32-residue alpha-helical peptide comprising the dimerization domain of HNF-1 was monitored by circular dichroism spectroscopy. The conformational stability of this peptide was shown to be concentration dependent, and the unfolding reaction is described as a two-state transition between folded dimers and unfolded monomers (PMID:1988015).
1f93
1g2y
1g2z
1g39
2gyp
MF2120020
Factor for inversion stimulation (FIS)
1ety
X-ray
2.00
homodimer
Escherichia coli
11183780
Cheng YS, Yang WZ, Johnson RC, Yuan HS
Structural analysis of the transcriptional activation region on Fis: crystal structures of six Fis mutants with different activation properties.
J. Mol. Biol.
2000
5
302
1139-51
The Fis protein regulates gene expression in Escherichia coli by activating or repressing transcription of a variety of genes. Fis can activate transcription when bound to DNA upstream of the RNA-polymerase-binding site, such as in the rrnB P1 promoter, or when bound to a site overlapping the -35 RNA polymerase binding site, such as in the proP P2 promoter. It has been suggested that transcriptional activation in both promoters results from interactions between specific amino acids within a turn connecting the B and C helices (the BC turn) in Fis and the C-terminal domain of the alpha-subunit of RNA polymerase (alphaCTD of RNAP). Here, crystal structures of six Fis BC turn mutants with different transcriptional activation properties, Q68A, R71Y, R71L, G72A, G72D and Q74A, were determined at 1.9 to 2.8 A resolution. Two of these mutants, R71Y and R71L, crystallized in unit cells which are different from that of wild-type Fis, and the structure of R71L offers the most complete Fis model to date in that the extended structure of the N-terminal region is revealed. The BC turn in all of these mutant structures remains in a nearly identical gamma gamma beta-turn conformation as present in wild-type Fis. Analyses of the molecular surfaces of the transactivation region of the mutants suggest that several residues in or near the BC turn, including Gln68, Arg71, Gly72 and Gln74, form a ridge that could contact the alphaCTD of RNAP on one side. The structures and biochemical properties of the mutants suggest that Arg71 is the most critical residue for contacting RNAP within this ridge and that the glycine at position 72 helps to stabilize the structure.
GO:0043565
sequence-specific DNA binding
GO:0005515
protein binding
GO:0003700
transcription factor activity, sequence-specific DNA binding
GO:0006355
regulation of transcription, DNA-templated
GO:0006351
transcription, DNA-templated
GO:0000787
cytoplasmic nucleosome
GO:0009295
nucleoid
GO:0005829
cytosol
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Other
Other
A
DNA-binding protein Fis
Escherichia coli
MFEQRVNSDVLTVSTVNSQDQVTQKPLRDSVKQALKNYFAQLNGQDVNDLYELVLAEVEQPLLDMVMQYTRGNQTRAALMMGINRGTLRKKLKKYGMN
98
P0A6R3
10
98
90.8%
UniRef90_A8AQG0
10
98
secondary structure
beta
23
23
secondary structure
beta
26
26
secondary structure
helix
27
39
secondary structure
helix
50
70
secondary structure
helix
74
81
secondary structure
helix
85
94
pfam
PF02954.16
HTH_8
54
95
B
DNA-binding protein Fis
Escherichia coli
MFEQRVNSDVLTVSTVNSQDQVTQKPLRDSVKQALKNYFAQLNGQDVNDLYELVLAEVEQPLLDMVMQYTRGNQTRAALMMGINRGTLRKKLKKYGMN
98
P0A6R3
6
98
94.9%
UniRef90_A8AQG0
6
98
secondary structure
beta
12
12
secondary structure
beta
26
26
secondary structure
helix
27
40
secondary structure
helix
50
69
secondary structure
helix
74
81
secondary structure
helix
85
94
pfam
PF02954.16
HTH_8
54
95
FIS forms an intertwined homodimer. Equilibrium and kinetic methods have shown that FIS follows a two-step folding reaction where the two unfolded monomers associate to a dimeric intermediate during a fast phase, which is followed by a slower, subsequent folding of the dimeric intermediate to the native dimer (PMID:14698300).
1etk
1eto
1etq
1etv
1etw
1etx
1f36
1fia
1fip
3fis
4fis
4ihv
4ihw
4ihx
4ihy
3iv5
3jr9
3jra
3jrb
3jrc
3jrd
3jre
3jrf
3jrg
3jrh
3jri
5ds9
5dtd
5e3l
5e3m
5e3n
5e3o
MF4410001
Neuronal SNARE core complex (Vamp2 / Syntaxin-1A / SNAP25)
1n7s
X-ray
1.45
heterotetramer
Rattus norvegicus
12496247
Ernst JA, Brunger AT
High resolution structure, stability, and synaptotagmin binding of a truncated neuronal SNARE complex.
J. Biol. Chem.
2003
10
278
8630-6
The structure of a truncated SNARE complex has been solved to 1.4-A resolution revealing a stabilizing salt bridge, sites of hydration, and conformational variability of the ionic central layer that were not observed in a previously published structure at 2.4-A resolution (Sutton, R. B., Fasshauer, D., Jahn, R., and Brunger, A. T. (1998) Nature 395, 347-353). The truncated complex lacks residues involved in phospholipid binding and denatures at a lower temperature than longer complexes as assessed by SDS and circular dichroism thermal melts. The truncated SNARE complex is monomeric, and it retains binding to synaptotagmin I.
GO:0048306
calcium-dependent protein binding
GO:0044325
ion channel binding
GO:0005484
SNAP receptor activity
GO:0017022
myosin binding
GO:0000149
SNARE binding
GO:0070044
synaptobrevin 2-SNAP-25-syntaxin-1a complex
GO:0070032
synaptobrevin 2-SNAP-25-syntaxin-1a-complexin I complex
GO:0030054
cell junction
GO:0043229
intracellular organelle
GO:0070033
synaptobrevin 2-SNAP-25-syntaxin-1a-complexin II complex
GO:0043005
neuron projection
GO:0045202
synapse
GO:0005886
plasma membrane
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
4
Coils and zippers
Coiled coil (tetrameric, 4-helix bundle)
A
Vesicle-associated membrane protein 2
Rattus norvegicus
GSNRRLQQTQAQVDEVVDIMRVNVDKVLERDQKLSELDDRADALQAGASQFETSAAKLKRKYW
63
P63045
27
89
54.3%
UniRef90_P63044
28
89
secondary structure
helix
29
88
pfam
PF00957.18
Synaptobrevin
28
116
B
Syntaxin-1A
Rattus norvegicus
GSALSEIETRHSEIIKLENSIRELHDMFMDMAMLVESQGEMIDRIEYNVEHAVDYVERAVSDTKKAVK
68
P32851
189
256
23.6%
UniRef90_P32851
191
256
secondary structure
helix
192
254
pfam
PF00804.22
Syntaxin
30
227
pfam
PF05739.16
SNARE
228
280
C
Synaptosomal-associated protein 25
Rattus norvegicus
GSMRNELEEMQRRADQLADESLESTRRMLQLVEESKDAGIRTLVMLDEQGEQLDRVEEGMNHINQDMKEAEKNLKDLGK
79
P60881
7
83
37.4%
UniRef90_P60880
7
83
secondary structure
helix
7
82
D
Synaptosomal-associated protein 25
Rattus norvegicus
GSARENEMDENLEQVSGIIGNLRHMALDMGNEIDTQNRQIDRIMEKADSNKTRIDEANQRATKMLG
66
P60881
139
204
32%
UniRef90_P60880
141
204
secondary structure
helix
142
201
The structure shows the core domain of a SNARE complex (PMID:12496247). SNARE complexes are formed by the parallel arrangement of four protein chains bound by coiled-coil interactions forming a four helix bundle (PMID:9390521). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
1kil
1sfc
2n1t
3hd7
3ipd
3rk2
3rk3
3rl0
5cch
5cci
5ccg
MF4400001
Autophagic SNARE core complex (Vamp8 / Syntaxin-17 / SNAP29)
4wy4
X-ray
1.40
heterotetramer
Homo sapiens
25686604
Diao J, Liu R, Rong Y, Zhao M, Zhang J, Lai Y, Zhou Q, Wilz LM, Li J, Vivona S, Pfuetzner RA, Brunger AT, Zhong Q
ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes.
Nature
2015
Autophagy, an important catabolic pathway implicated in a broad spectrum of human diseases, begins by forming double membrane autophagosomes that engulf cytosolic cargo and ends by fusing autophagosomes with lysosomes for degradation. Membrane fusion activity is required for early biogenesis of autophagosomes and late degradation in lysosomes. However, the key regulatory mechanisms of autophagic membrane tethering and fusion remain largely unknown. Here we report that ATG14 (also known as beclin-1-associated autophagy-related key regulator (Barkor) or ATG14L), an essential autophagy-specific regulator of the class III phosphatidylinositol 3-kinase complex, promotes membrane tethering of protein-free liposomes, and enhances hemifusion and full fusion of proteoliposomes reconstituted with the target (t)-SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) syntaxin 17 (STX17) and SNAP29, and the vesicle (v)-SNARE VAMP8 (vesicle-associated membrane protein 8). ATG14 binds to the SNARE core domain of STX17 through its coiled-coil domain, and stabilizes the STX17-SNAP29 binary t-SNARE complex on autophagosomes. The STX17 binding, membrane tethering and fusion-enhancing activities of ATG14 require its homo-oligomerization by cysteine repeats. In ATG14 homo-oligomerization-defective cells, autophagosomes still efficiently form but their fusion with endolysosomes is blocked. Recombinant ATG14 homo-oligomerization mutants also completely lose their ability to promote membrane tethering and to enhance SNARE-mediated fusion in vitro. Taken together, our data suggest an autophagy-specific membrane fusion mechanism in which oligomeric ATG14 directly binds to STX17-SNAP29 binary t-SNARE complex on autophagosomes and primes it for VAMP8 interaction to promote autophagosome-endolysosome fusion.
GO:0005484
SNAP receptor activity
GO:0006810
transport
GO:0097352
autophagosome maturation
GO:0031201
SNARE complex
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
4
Coils and zippers
Coiled coil (tetrameric, 4-helix bundle)
A
Vesicle-associated membrane protein 8
Homo sapiens
DRVRNLQSEVEGVKNIMTQNVERILARGENLEHLRNKTEDLEATSEHFKTTSQKVARKFWWKNV
64
Q9BV40
11
74
64%
UniRef90_Q9BV40
11
74
secondary structure
helix
12
72
pfam
PF00957.18
Synaptobrevin
9
97
B
Syntaxin-17
Homo sapiens
ESWETLEADLIELSQLVTDFSLLVNSQQEKIDSIADHVNSAAVNVEEGTKNLGKAAKY
58
P56962
170
227
19.2%
UniRef90_P56962
170
227
secondary structure
helix
173
195
secondary structure
helix
197
226
C
Synaptosomal-associated protein 29
Homo sapiens
ADRQQYLRQEVLRRAEATAASTSRSLALMYESEKVGVASSEELARQRGVLERTEKMVDKMDQDLKISQKHINSIKSVF
78
O95721
39
116
30.2%
UniRef90_O95721
39
116
secondary structure
helix
40
113
pfam
PF12352.5
V-SNARE_C
52
114
D
Synaptosomal-associated protein 29
Homo sapiens
HLRAYHQKIDSNLDELSMGLGRLKDIALGMQTEIEEQDDILDRLTTKVDKLDVNIKSTERKVRQL
65
O95721
194
258
25.2%
UniRef90_O95721
194
258
secondary structure
helix
195
251
secondary structure
helix
254
256
The structure shows the core domain of a SNARE complex (PMID:25686604). SNARE complexes are formed by the parallel arrangement of four protein chains bound by coiled-coil interactions forming a four helix bundle (PMID:9390521). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
MF4411001
Endosomal SNARE core complex (Vamp4 / Vti1-rp2 / Syntaxin-6 / Syntaxin-13)
2nps
X-ray
2.50
heterotetramer
Mus musculus / Rattus norvegicus / Pongo abelii
17159904
Zwilling D, Cypionka A, Pohl WH, Fasshauer D, Walla PJ, Wahl MC, Jahn R
Early endosomal SNAREs form a structurally conserved SNARE complex and fuse liposomes with multiple topologies.
EMBO J.
2007
1
26
9-18
SNARE proteins mediate membrane fusion in eukaryotic cells. They contain conserved SNARE motifs that are usually located adjacent to a C-terminal transmembrane domain. SNARE motifs spontaneously assemble into four helix bundles, with each helix belonging to a different subfamily. Liposomes containing SNAREs spontaneously fuse with each other, but it is debated how the SNAREs are distributed between the membranes. Here, we report that the SNAREs mediating homotypic fusion of early endosomes fuse liposomes in five out of seven possible combinations, in contrast to previously studied SNAREs involved in heterotypic fusion events. The crystal structure of the early endosomal SNARE complex resembles that of the neuronal and late endosomal complexes, but differs in surface side-chain interactions. We conclude that homotypic fusion reactions may proceed with multiple SNARE topologies, suggesting that the conserved SNARE structure allows for flexibility in the initial interactions needed for fusion.
GO:0005484
SNAP receptor activity
GO:0016192
vesicle-mediated transport
GO:0005794
Golgi apparatus
GO:0016021
integral component of membrane
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
4
Coils and zippers
Coiled coil (tetrameric, 4-helix bundle)
A
Vesicle-associated membrane protein 4
Mus musculus
GSMGPRNDKIKHVQNQVDEVIDVMQENITKVIERGERLDELQDKSESLSDNATAFSNRSKQLRRQMWWRGCKIK
74
O70480
44
117
52.5%
UniRef90_O75379
46
117
secondary structure
helix
54
57
secondary structure
helix
60
109
pfam
PF00957.18
Synaptobrevin
49
137
B
Syntaxin-12
Rattus norvegicus
GSMRETAIQQLEADILDVNQIFKDLAMMIHDQGDLIDSIEANVESSEVHVERASDQLQRAAYYQKKSRKKM
71
G3V7P1
181
251
25.9%
UniRef90_Q86Y82
184
251
secondary structure
helix
184
245
pfam
PF05739.16
SNARE
214
266
C
Vesicle transport through interaction with t-SNAREs homolog 1A
Rattus norvegicus
GSMRAHLLDNTERLERSSRRLEAGYQIAVETEQIGQEMLENLSHDRERIQRARERLRETDANLGKSSRILTGMLRRIIQNR
81
Q9JI51
119
199
36.2%
UniRef90_Q9JI51
122
199
secondary structure
helix
124
136
secondary structure
helix
138
194
pfam
PF12352.5
V-SNARE_C
130
195
D
Syntaxin-6
Pongo abelii
GSHMASMTGGNNMGRMQDEQLELVSGSIGVLKNMSQRIGGELEEQAVMLEDFSHELESTQSRLDNVMKKLAKVSHMTSDRRQ
82
Q5R6Q2
169
234
25.9%
UniRef90_O43752
169
234
secondary structure
helix
173
229
pfam
PF05739.16
SNARE
199
251
The structure shows the core domain of a SNARE complex (PMID:17159904). SNARE complexes are formed by the parallel arrangement of four protein chains bound by coiled-coil interactions forming a four helix bundle (PMID:9390521). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
MF4411002
Endosomal SNARE core complex (Vamp8 / Vti1-rp1 / Syntaxin-7 / Syntaxin-8)
1gl2
X-ray
1.9
heterotetramer
Rattus norvegicus / Mus musculus
11786915
Antonin W, Fasshauer D, Becker S, Jahn R, Schneider TR
Crystal structure of the endosomal SNARE complex reveals common structural principles of all SNAREs.
Nat. Struct. Biol.
2002
2
9
107-11
SNARE proteins are crucial for intracellular membrane fusion in all eukaryotes. These proteins assemble into tight complexes that connect membranes and may induce fusion. The crystal structure of the neuronal core complex is represented by an unusually long bundle of four alpha-helices connected by 16 layers of mostly hydrophobic amino acids. Here we report the 1.9 A resolution crystal structure of an endosomal SNARE core complex containing four SNAREs: syntaxin 7, syntaxin 8, vti1b and endobrevin/VAMP-8. Despite limited sequence homology, the helix alignment and the layer structure of the endosomal complex are remarkably similar to those of the neuronal complex. However, subtle variations are evident that characterize different SNARE subfamilies. We conclude that the structure of the SNARE core complex is an evolutionarily conserved hallmark of all SNARE complexes and is intimately associated with the general role of SNAREs in membrane fusion.
GO:0005484
SNAP receptor activity
GO:0016192
vesicle-mediated transport
GO:0005765
lysosomal membrane
GO:0016021
integral component of membrane
GO:0031201
SNARE complex
GO:0055037
recycling endosome
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
4
Coils and zippers
Coiled coil (tetrameric, 4-helix bundle)
A
Vesicle-associated membrane protein 8
Rattus norvegicus
GSHMSAGNDRVRNLQSEVEGVKNIMTQNVERILARGENLDHLRNKTEDLEATSEHFKTTSQKVAR
65
Q9WUF4
2
66
65%
UniRef90_O70404
7
67
secondary structure
helix
12
62
pfam
PF00957.18
Synaptobrevin
8
96
B
Syntaxin-7
Mus musculus
GSHMHERESSIRQLEADIMDINEIFKDLGMMIHEQGDVIDSIEANVESAEVHVQQANQQLSRAAN
65
O70439
165
229
24.9%
UniRef90_O15400
168
229
secondary structure
helix
170
226
pfam
PF05739.16
SNARE
201
255
C
Vesicle transport through interaction with t-SNAREs homolog 1B
Mus musculus
GSHMNRATQSIERSHRIATETDQIGTEIIEELGEQRDQLERTKSRLVNTNENLSKSRKILRSMSR
65
O88384
136
200
28%
UniRef90_O88384
139
200
secondary structure
helix
141
196
pfam
PF12352.5
V-SNARE_C
137
202
D
Syntaxin-8
Rattus norvegicus
GSHMQEQDAGLDALSSIISRQKQMGQEIGNELDEQNEIIDDLANLVENTDEKLRTEARRVTLVDR
65
Q9Z2Q7
145
209
27.5%
UniRef90_Q9Z2Q7
152
209
secondary structure
helix
153
204
pfam
PF05739.16
SNARE
181
233
The structure shows the core domain of a SNARE complex (PMID:11786915). SNARE complexes are formed by the parallel arrangement of four protein chains bound by coiled-coil interactions forming a four helix bundle (PMID:9390521). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
MF4411003
Neuronal SNARE core complex (Syntaxin-binding protein 5 / Syntaxin-1A / SNAP25)
1urq
X-ray
2.0
heterotetramer
Rattus norvegicus / Macaca mulatta
15316007
Pobbati AV, Razeto A, Böddener M, Becker S, Fasshauer D
Structural basis for the inhibitory role of tomosyn in exocytosis.
J. Biol. Chem.
2004
45
279
47192-200
Upon Ca2+ influx synaptic vesicles fuse with the plasma membrane and release their neurotransmitter cargo into the synaptic cleft. Key players during this process are the Q-SNAREs syntaxin 1a and SNAP-25 and the R-SNARE synaptobrevin 2. It is thought that these membrane proteins gradually assemble into a tight trans-SNARE complex between vesicular and plasma membrane, ultimately leading to membrane fusion. Tomosyn is a soluble protein of 130 kDa that contains a COOH-terminal R-SNARE motif but lacks a transmembrane anchor. Its R-SNARE motif forms a stable core SNARE complex with syntaxin 1a and SNAP-25. Here we present the crystal structure of this core tomosyn SNARE complex at 2.0-A resolution. It consists of a four-helical bundle very similar to that of the SNARE complex containing synaptobrevin. Most differences are found on the surface, where they prevented tight binding of complexin. Both complexes form with similar rates as assessed by CD spectroscopy. In addition, synaptobrevin cannot displace the tomosyn helix from the tight complex and vice versa, indicating that both SNARE complexes represent end products. Moreover, data bank searches revealed that the R-SNARE motif of tomosyn is highly conserved throughout all eukaryotic kingdoms. This suggests that the formation of a tight SNARE complex is important for the function of tomosyn.
GO:0006887
exocytosis
GO:0045202
synapse
GO:0031201
SNARE complex
GO:0005886
plasma membrane
GO:0030054
cell junction
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
4
Coils and zippers
Coiled coil (tetrameric, 4-helix bundle)
A
Syntaxin-binding protein 5
Rattus norvegicus
GSHGGIEGVKGAASGVVGELARARLALDERGQKLSDLEERTAAMMSSADSFSKHAHEMMLKYK
63
Q9WU70
1083
1145
5.5%
UniRef90_Q9WU70
1086
1145
secondary structure
helix
1088
1142
B
Syntaxin-1A
Rattus norvegicus
GSHSKQALSEIETRHSEIIKLENSIRELHDMFMDMAMLVESQGEMIDRIEYNVEHAVDYVERAVSDTKKAVKYQS
75
P32851
185
259
26%
UniRef90_P32851
186
259
secondary structure
helix
197
256
pfam
PF00804.22
Syntaxin
30
227
pfam
PF05739.16
SNARE
228
280
C
Synaptosomal-associated protein 25
Rattus norvegicus
GSHMRNELEEMQRRADQLADESLESTRRMLQLVEESKDAGIRTLVMLDEQGEQLDRVEEGMNHINQDMKEAEKNLKDLGK
80
P60881
5
83
38.3%
UniRef90_P60880
5
83
secondary structure
helix
17
80
D
Synaptosomal-associated protein 25
Macaca mulatta
GSHMASRENEMDENLEQVSGIIGNLRHMALDMGNEIDTQNRQIDRIMEKADSNKTRIDEANQRATKMLG
69
P60881
141
204
31.1%
UniRef90_P60880
141
204
secondary structure
helix
141
198
The structure shows the core domain of a SNARE complex (PMID:15316007). SNARE complexes are formed by the parallel arrangement of four protein chains bound by coiled-coil interactions forming a four helix bundle (PMID:9390521). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
MF4410002
Exocytotic SNARE core complex (Synaptobrevin homolog 1 / SSO1 / Protein transport protein SEC9)
3b5n
X-ray
1.60
heterotetramer
Saccharomyces cerevisiae
17956869
Strop P, Kaiser SE, Vrljic M, Brunger AT
The structure of the yeast plasma membrane SNARE complex reveals destabilizing water-filled cavities.
J. Biol. Chem.
2008
2
283
1113-9
SNARE proteins form a complex that leads to membrane fusion between vesicles, organelles, and plasma membrane in all eukaryotic cells. We report the 1.7A resolution structure of the SNARE complex that mediates exocytosis at the plasma membrane in the yeast Saccharomyces cerevisiae. Similar to its neuronal and endosomal homologues, the S. cerevisiae SNARE complex forms a parallel four-helix bundle in the center of which is an ionic layer. The S. cerevisiae SNARE complex exhibits increased helix bending near the ionic layer, contains water-filled cavities in the complex core, and exhibits reduced thermal stability relative to mammalian SNARE complexes. Mutagenesis experiments suggest that the water-filled cavities contribute to the lower stability of the S. cerevisiae complex.
GO:0005484
SNAP receptor activity
GO:0006906
vesicle fusion
GO:0031201
SNARE complex
Chains E, F, G, H, I, J, K and L were removed as chains A, B, C and D represent the biologically active tetramer.
4
4
Coils and zippers
Coiled coil (tetrameric, 4-helix bundle)
A
Synaptobrevin homolog 1
Saccharomyces cerevisiae
GSRTAELQAEIDDTVGIMRDNINKVAERGERLTSIEDKADNLAVSAQGFKRGANRVRKAMW
61
P31109
26
86
52.1%
UniRef90_P31109
27
86
secondary structure
helix
27
85
pfam
PF00957.18
Synaptobrevin
25
113
B
Protein SSO1
Saccharomyces cerevisiae
ALAEVQARHQELLKLEKSMAELTQLFNDMEELVIEQQENVDVIDKNVEDAQLDVEQGVGHTDKAVKSAR
69
P32867
189
257
23.8%
UniRef90_P32867
189
257
secondary structure
helix
190
256
pfam
PF00804.22
Syntaxin
33
226
pfam
PF05739.16
SNARE
226
278
C
Protein transport protein SEC9
Saccharomyces cerevisiae
GSIKFTKQSSVASTRNTLKMAQDAERAGMNTLGMLGHQSEQLNNVEGNLDLMKVQNKVADEKVAELKKLQ
70
P40357
431
500
10.8%
UniRef90_P40357
433
499
secondary structure
helix
433
499
D
Protein transport protein SEC9
Saccharomyces cerevisiae
GSEMELEIDRNLDQIQQVSNRLKKMALTTGKELDSQQKRLNNIEESTDDLDINLHMNTNRLAGI
64
P40357
587
650
9.8%
UniRef90_P40357
596
650
secondary structure
helix
596
648
The structure shows the core domain of a SNARE complex (PMID:17956869). SNARE complexes are formed by the parallel arrangement of four protein chains bound by coiled-coil interactions forming a four helix bundle (PMID:9390521). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
MF4210003
Endosomal SNARE core complex (Syntaxin-1A / SNAP25)
1jth
X-ray
2.00
heterotetramer
Rattus norvegicus
11533035
Misura KM, Gonzalez LC, May AP, Scheller RH, Weis WI
Crystal structure and biophysical properties of a complex between the N-terminal SNARE region of SNAP25 and syntaxin 1a.
J. Biol. Chem.
2001
44
276
41301-9
SNARE proteins are required for intracellular membrane fusion. In the neuron, the plasma membrane SNAREs syntaxin 1a and SNAP25 bind to VAMP2 found on neurotransmitter-containing vesicles. These three proteins contain "SNARE regions" that mediate their association into stable tetrameric coiled-coil structures. Syntaxin 1a contributes one such region, designated H3, and SNAP25 contributes two SNARE regions to the fusogenic complex with VAMP2. Syntaxin 1a H3 (syn1aH3) and SNAP25 can form a stable assembly, which can then be bound by VAMP2 to form the full SNARE complex. Here we show that syn1aH3 can also form a stable but kinetically trapped complex with the N-terminal SNARE region of SNAP25 (S25N). The crystal structure of this complex reveals an extended parallel four-helix bundle similar to that of the core SNARE and the syn1aH3-SNAP25 complexes. The inherent ability of syn1aH3 and S25N to associate stably in vitro implies that the intracellular fusion machinery must prevent formation of, or remove, any non-productive complexes. Comparison with the syn1aH3-SNAP25 complex suggests that the linkage of the N- and C-terminal SNAP25 SNARE regions is kinetically advantageous in preventing formation of the non-productive syn1aH3-S25N complex. We also demonstrate that the syn1aH3-S25N complex can be disassembled by alpha-SNAP and N-ethylmaleimide-sensitive factor.
GO:0019904
protein domain specific binding
GO:0000149
SNARE binding
GO:0017022
myosin binding
GO:0047485
protein N-terminus binding
GO:0005484
SNAP receptor activity
GO:0044325
ion channel binding
GO:0048306
calcium-dependent protein binding
GO:0031629
synaptic vesicle fusion to presynaptic active zone membrane
GO:0005886
plasma membrane
GO:0045202
synapse
GO:0070033
synaptobrevin 2-SNAP-25-syntaxin-1a-complexin II complex
GO:0043005
neuron projection
GO:0043229
intracellular organelle
GO:0070032
synaptobrevin 2-SNAP-25-syntaxin-1a-complexin I complex
GO:0030054
cell junction
GO:0070044
synaptobrevin 2-SNAP-25-syntaxin-1a complex
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
2
Coils and zippers
Coiled coil (tetrameric, 4-helix bundle)
A
Synaptosomal-associated protein 25
Rattus norvegicus
MAEDADMRNELEEMQRRADQLADESLESTRRMLQLVEESKDAGIRTLVMLDEQGEQLERIEEGMDQINKDMKEAEKNLTDLG
82
P60881
1
82
39.8%
UniRef90_P60880
1
82
secondary structure
helix
12
71
B
Syntaxin-1A
Rattus norvegicus
ALSEIETRHSEIIKLENSIRELHDMFMDMAMLVESQGEMIDRIEYNVEHAVDYVERAVSDTKKAVKYQSKARRKKIM
77
P32851
191
267
26.7%
UniRef90_P32851
191
267
secondary structure
helix
192
256
pfam
PF00804.22
Syntaxin
30
227
pfam
PF05739.16
SNARE
228
280
C
Synaptosomal-associated protein 25
Rattus norvegicus
MAEDADMRNELEEMQRRADQLADESLESTRRMLQLVEESKDAGIRTLVMLDEQGEQLERIEEGMDQINKDMKEAEKNLTDLG
82
P60881
1
82
39.8%
UniRef90_P60880
1
82
secondary structure
helix
11
77
D
Syntaxin-1A
Rattus norvegicus
ALSEIETRHSEIIKLENSIRELHDMFMDMAMLVESQGEMIDRIEYNVEHAVDYVERAVSDTKKAVKYQSKARRKKIM
77
P32851
191
267
26.7%
UniRef90_P32851
191
267
secondary structure
helix
196
244
pfam
PF00804.22
Syntaxin
30
227
pfam
PF05739.16
SNARE
228
280
The structure shows the core domain of a SNARE complex (PMID:11533035). SNARE complexes are formed by the parallel arrangement of four protein chains bound by coiled-coil interactions forming a four helix bundle (PMID:9390521). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
MF2200010
CENP-A/histone H4 dimer (human)
3nqj
X-ray
2.10
heterodimer
Homo sapiens
20739937
Sekulic N, Bassett EA, Rogers DJ, Black BE
The structure of (CENP-A-H4)(2) reveals physical features that mark centromeres.
Nature
2010
7313
467
347-51
Centromeres are specified epigenetically, and the histone H3 variant CENP-A is assembled into the chromatin of all active centromeres. Divergence from H3 raises the possibility that CENP-A generates unique chromatin features to mark physically centromere location. Here we report the crystal structure of a subnucleosomal heterotetramer, human (CENP-A-H4)(2), that reveals three distinguishing properties encoded by the residues that comprise the CENP-A targeting domain (CATD; ref. 2): (1) a CENP-A-CENP-A interface that is substantially rotated relative to the H3-H3 interface; (2) a protruding loop L1 of the opposite charge as that on H3; and (3) strong hydrophobic contacts that rigidify the CENP-A-H4 interface. Residues involved in the CENP-A-CENP-A rotation are required for efficient incorporation into centromeric chromatin, indicating specificity for an unconventional nucleosome shape. DNA topological analysis indicates that CENP-A-containing nucleosomes are octameric with conventional left-handed DNA wrapping, in contrast to other recent proposals. Our results indicate that CENP-A marks centromere location by restructuring the nucleosome from within its folded histone core.
GO:0046982
protein heterodimerization activity
GO:0003677
DNA binding
GO:0034080
CENP-A containing nucleosome assembly
GO:0005654
nucleoplasm
GO:0000786
nucleosome
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
2
Histone-like interactions
Histone-like complexes
A
Histone H3-like centromeric protein A
Homo sapiens
MLLIRKLPFSRLAREICVKFTRGVDFNWQAQALLALQEAAEAFLVHLFEDAYLLTLHAGRVTLFPKDVQLARRIRGLEEGLG
82
P49450
59
140
58.6%
UniRef90_P49450
60
140
secondary structure
helix
64
79
secondary structure
beta
85
86
secondary structure
helix
88
115
secondary structure
beta
121
121
secondary structure
helix
123
133
pfam
PF00125.21
Histone
2
133
B
Histone H4
Homo sapiens
MKVLRDNIQGITKPAIRRLARRGGVKRISGLIYEETRGVLKVFLENVIRDAVTYTEHAKRKTVTAMDVVYALKRQGRTLYGFGG
84
P62805
20
103
81.6%
UniRef90_P62805
21
103
secondary structure
helix
27
29
secondary structure
helix
32
41
secondary structure
beta
47
47
secondary structure
helix
51
76
secondary structure
beta
81
82
secondary structure
helix
84
91
pfam
PF15511.3
CENP-T_C
18
99
The structure shows a dimer adopting the histone fold with Centromere protein A (CENP-A) substituting histone H3 in a classical H3/H4 dimer (PMID:20739937). While CENP-A containing dimers show slight structural differences compared to H3/H4 dimers, the overall dimer and nucleosomal structure (and based on these presumably the folding kinetics) are essentially the same (PMID:22127263). Histone dimerization has been experimentally characterized to be coupled to the structure formation of both interacting partners (PMID:12779337); this synergistic folding has been shown separately for various histone dimers (PMID:15588829, PMID:15096635). Histones containing various types of monomeric subunits can exhibit varying stability and folding kinetics; however, independent of composition and folding kinetics, all histones appear to fold in a cooperative fashion that is coupled to binding (PMID:11669650).
3an2
3nqu
3r45
3wtp
MF2210006
CENP-A/histone H4 dimer (Kluyveromyces lactis)
2yfw
X-ray
2.60
heterodimer
Kluyveromyces lactis
21606327
Cho US, Harrison SC
Recognition of the centromere-specific histone Cse4 by the chaperone Scm3.
Proc. Natl. Acad. Sci. U.S.A.
2011
23
108
9367-71
A specialized nucleosome is a component of all eukaryotic kinetochores. The core of this nucleosome contains a centromere-specific histone, CENP-A (the Cse4 gene product in budding yeast), instead of the usual H3. Assembly of a centromeric nucleosome depends on a specific chaperone, called Scm3 in yeast and HJURP in higher eukaryotes. We describe here the structure of a complex formed by an N-terminal fragment of Scm3 with the histone-fold domains of Cse4, and H4, all prepared as recombinant proteins derived from the budding yeast Kluyveromyces lactis. The contacts of Scm3 with Cse4 explain its selectivity for the centromere-specific histone; key residues at the interface are conserved in HJURP, indicating a common mechanism for centromeric-histone deposition. We also report the structure of a (Cse4 : H4)(2) heterotetramer; comparison with the structure of the Scm3:Cse4:H4 complex shows that tetramer formation and DNA-binding require displacement of Scm3 from the nucleosome core. The two structures together suggest that specific contacts between the chaperone and Cse4, rather than an altered overall structure of the nucleosome core, determine the selective presence of Cse4 at centromeres.
GO:0003677
DNA binding
GO:0046982
protein heterodimerization activity
GO:0005634
nucleus
GO:0000786
nucleosome
Chains C, D, E, F, G and H were removed as chains A and B represent the biologically relevant dimer.
2
2
Histone-like interactions
Histone-like complexes
A
Histone H3-like centromeric protein CSE4
Kluyveromyces lactis
ALAEIRKYQRSTDLLISRMPFARLVKEVTDQFTTESEPLRWQSMAIMALQEASEAYLVGLLEHTNLLALHAKRITIMRKDMQLARRIRGQFI
92
Q6CTI2
93
184
50%
UniRef90_Q6CTI2
93
184
secondary structure
helix
110
124
secondary structure
beta
132
133
secondary structure
helix
135
162
secondary structure
beta
167
168
secondary structure
helix
170
180
pfam
PF00125.21
Histone
45
180
B
Histone H4
Kluyveromyces lactis
MSGRGKGGKGLGKGGAKRHRKILRDNIQGITKPAIRRLARRGGVKRISGLIYEEVRNVLKTFLESVIRDAVTYTEHAKRKTVTSLDVVYALKRQGRTLYGFGG
103
Q6CMU6
1
103
100%
UniRef90_P02309
18
103
secondary structure
helix
32
41
secondary structure
beta
46
47
secondary structure
helix
51
76
secondary structure
beta
81
82
secondary structure
helix
84
94
pfam
PF15511.3
CENP-T_C
19
99
The structure shows a dimer adopting the histone fold with Centromere protein A (CENP-A) substituting histone H3 in a classical H3/H4 dimer (PMID:21606327). While CENP-A containing dimers show slight structural differences compared to H3/H4 dimers, the overall dimer and nucleosomal structure (and based on these presumably the folding kinetics) are essentially the same (PMID:22127263). Histone dimerization has been experimentally characterized to be coupled to the structure formation of both interacting partners (PMID:12779337); this synergistic folding has been shown separately for various histone dimers (PMID:15588829, PMID:15096635). Histones containing various types of monomeric subunits can exhibit varying stability and folding kinetics; however, independent of composition and folding kinetics, all histones appear to fold in a cooperative fashion that is coupled to binding (PMID:11669650).
2yfv
MF2200011
CENP-S/CENP-X dimer (human)
4ne3
X-ray
1.80
heterodimer
Homo sapiens
24390579
Zhao Q, Saro D, Sachpatzidis A, Singh TR, Schlingman D, Zheng XF, Mack A, Tsai MS, Mochrie S, Regan L, Meetei AR, Sung P, Xiong Y
The MHF complex senses branched DNA by binding a pair of crossover DNA duplexes.
Nat Commun
2014
5
2987
The conserved MHF1-MHF2 (MHF) complex functions in the activation of the Fanconi anaemia pathway of the DNA damage response, in regulating homologous recombination, and in DNA replication fork maintenance. MHF facilitates the processing of multiple types of branched DNAs by the DNA translocase FANCM. Here we report the crystal structure of a human MHF-DNA complex that reveals the DNA-binding mode of MHF. The structure suggests that MHF prefers branched DNA over double-stranded DNA because it engages two duplex arms. Biochemical analyses verify that MHF preferentially engages DNA forks or various four-way junctions independent of the junction-site structure. Furthermore, genetic experiments provide evidence that the observed DNA-binding interface of MHF is important for cellular resistance to DNA damage. These results offer insights into how the MHF complex recognizes branched DNA and stimulates FANCM activity at such a structure to promote genome maintenance.
GO:0003677
DNA binding
GO:0005515
protein binding
GO:0034080
CENP-A containing nucleosome assembly
GO:0036297
interstrand cross-link repair
GO:0051382
kinetochore assembly
GO:0000712
resolution of meiotic recombination intermediates
GO:0031297
replication fork processing
GO:0007067
mitotic nuclear division
GO:0051301
cell division
GO:0031398
positive regulation of protein ubiquitination
GO:0000777
condensed chromosome kinetochore
GO:0043240
Fanconi anaemia nuclear complex
GO:0071821
FANCM-MHF complex
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
2
Histone-like interactions
Histone-like complexes
A
Centromere protein S
Homo sapiens
SYQQRLKAAVHYTVGCLCEEVALDKAMQFSKQTIAAISELTFRQCENFAKDLEMFARHAKRTTINTEDVKLLARRSNSLLKYITDKSEEIAQA
93
Q8N2Z9
14
106
67.4%
UniRef90_Q8N2Z9
14
105
secondary structure
helix
15
38
secondary structure
beta
43
43
secondary structure
helix
45
66
secondary structure
helix
68
73
secondary structure
beta
78
79
secondary structure
helix
81
87
secondary structure
helix
92
105
pfam
PF15630.3
CENP-S
17
92
B
Centromere protein X
Homo sapiens
SGFRKELVSRLLHLHFKDDKTKVSGDALQLMVELLKVFVVEAAVRGVRQAQAEDALRVDVDQLEKVLPQLLLDF
74
A8MT69
8
81
91.4%
UniRef90_A8MT69
8
81
secondary structure
helix
12
20
secondary structure
beta
29
30
secondary structure
helix
32
37
secondary structure
helix
39
60
secondary structure
beta
66
66
secondary structure
helix
68
81
pfam
PF09415.7
CENP-X
12
81
Centromere proteins S and X (CENP-S and CENP-X), also called MHF1 and MHF2 form histone-like heterodimers (PMID:20347428). These dimers further associate with heterodimers formed by CENP-T and CENP-W and these tetrameric structures share a high degree of similarity with canonical histone multimers within the nucleosome (PMID:22304917). CENP-T-W-S-X tetramers - similarly to nucleosomes formed by histones - are able to bind and supercoil DNA (PMID:24234442). Apart from some structural differences leading to different functions (e.g. CENP-T-W-S-X tetramers show a preference for branched DNA as opposed to nucleosomes, PMID:24390579), both the overall and the underlying basic structures of nucleosomes and CENP-T-W-S-X tetramers are essentially the same with both CENP-S/CENP-X and CENP-T/W dimers forming structures nearly identical to that of histone dimers (PMID:20347428 and PMID:19070575). Histone dimerization has been experimentally characterized to be coupled to the structure formation of both interacting partners (PMID:12779337); this synergistic folding has been shown separately for various histone dimers (PMID:15588829, PMID:15096635). Histones containing various types of monomeric subunits can exhibit varying stability and folding kinetics; however, independent of composition and folding kinetics, all histones appear to fold in a cooperative fashion that is coupled to binding (PMID:11669650).
4dra
4drb
4e44
4e45
4ne5
4ne6
4ndy
4ne1
MF2210007
CENP-S/CENP-X dimer (Gallus gallus)
3b0b
X-ray
2.15
heterodimer
Gallus gallus
22304917
Nishino T, Takeuchi K, Gascoigne KE, Suzuki A, Hori T, Oyama T, Morikawa K, Cheeseman IM, Fukagawa T
CENP-T-W-S-X forms a unique centromeric chromatin structure with a histone-like fold.
Cell
2012
3
148
487-501
The multiprotein kinetochore complex must assemble at a specific site on each chromosome to achieve accurate chromosome segregation. Defining the nature of the DNA-protein interactions that specify the position of the kinetochore and provide a scaffold for kinetochore formation remain key goals. Here, we demonstrate that the centromeric histone-fold-containing CENP-T-W and CENP-S-X complexes coassemble to form a stable CENP-T-W-S-X heterotetramer. High-resolution structural analysis of the individual complexes and the heterotetramer reveals similarity to other histone fold-containing complexes including canonical histones within a nucleosome. The CENP-T-W-S-X heterotetramer binds to and supercoils DNA. Mutants designed to compromise heterotetramerization or the DNA-protein contacts around the heterotetramer strongly reduce the DNA binding and supercoiling activities in vitro and compromise kinetochore assembly in vivo. These data suggest that the CENP-T-W-S-X complex forms a unique nucleosome-like structure to generate contacts with DNA, extending the "histone code" beyond canonical nucleosome proteins.
GO:0003677
DNA binding
GO:0046982
protein heterodimerization activity
GO:0051301
cell division
GO:0007067
mitotic nuclear division
GO:0006281
DNA repair
GO:0051382
kinetochore assembly
GO:0000777
condensed chromosome kinetochore
GO:0005634
nucleus
Chains B and C were removed as chains A and D represent the biologically relevant dimer.
2
2
Histone-like interactions
Histone-like complexes
A
Centromere protein S
Gallus gallus
GSEAAGGEQRELLIQRLRAAVHYTTGCLCQDVAEDKGVLFSKQTVAAISEITFRQCENFARDLEMFARHAKRSTITSEDVKLLARRSNSLLKYITQKSDELASSNME
107
E1BSW7
2
106
75.5%
UniRef90_E1BSW7
2
106
secondary structure
helix
6
34
secondary structure
beta
38
39
secondary structure
helix
41
63
secondary structure
helix
65
69
secondary structure
beta
74
75
secondary structure
helix
77
83
secondary structure
helix
88
101
pfam
PF15630.3
CENP-S
14
89
D
Centromere protein X
Gallus gallus
GYEEREGGFRKETVERLLRLHFRDGRTRVNGDALLLMAELLKVFVREAAARAARQAQAEDLEKVDIEHVEKVLPQLLLDFV
81
P0DJH7
2
80
98.8%
UniRef90_P0DJH7
2
80
secondary structure
helix
10
20
secondary structure
beta
27
28
secondary structure
helix
30
35
secondary structure
helix
37
58
secondary structure
beta
63
64
secondary structure
helix
66
80
pfam
PF09415.7
CENP-X
10
79
Centromere proteins S and X (CENP-S and CENP-X), also called MHF1 and MHF2 form histone-like heterodimers (PMID:20347428). These dimers further associate with heterodimers formed by CENP-T and CENP-W and these tetrameric structures share a high degree of similarity with canonical histone multimers within the nucleosome (PMID:22304917). CENP-T-W-S-X tetramers - similarly to nucleosomes formed by histones - are able to bind and supercoil DNA (PMID:24234442). Apart from some structural differences leading to different functions (e.g. CENP-T-W-S-X tetramers show a preference for branched DNA as opposed to nucleosomes, PMID:24390579), both the overall and the underlying basic structures of nucleosomes and CENP-T-W-S-X tetramers are essentially the same with both CENP-S/CENP-X and CENP-T/W dimers forming structures nearly identical to that of histone dimers (PMID:20347428 and PMID:19070575). Histone dimerization has been experimentally characterized to be coupled to the structure formation of both interacting partners (PMID:12779337); this synergistic folding has been shown separately for various histone dimers (PMID:15588829, PMID:15096635). Histones containing various types of monomeric subunits can exhibit varying stability and folding kinetics; however, independent of composition and folding kinetics, all histones appear to fold in a cooperative fashion that is coupled to binding (PMID:11669650).
3vh5
3vh6
MF2210008
MHF complex (Saccharomyces cerevisiae)
3v9r
X-ray
2.40
heterodimer
Saccharomyces cerevisiae
22325783
Yang H, Zhang T, Tao Y, Wu L, Li HT, Zhou JQ, Zhong C, Ding J
Saccharomyces cerevisiae MHF complex structurally resembles the histones (H3-H4)₂ heterotetramer and functions as a heterotetramer.
Structure
2012
2
20
364-70
Fanconi anemia (FA) is a chromosomal instability disorder associated with deficiencies in the Fanconi anemia complementation group (FANC) network. A complex consisting of FANCM-associated histone-fold proteins 1 and 2 (MHF1 and MHF2) has been shown to act cooperatively with FANCM in DNA damage repair in the FA pathway. Here we report the structure of Saccharomyces cerevisiae MHF complex in which MHF1 and MHF2 assume a typical histone fold, and the complex has a heterotetrameric architecture similar to that of the histones (H3-H4)₂ heterotetramer. Loop L2 of MHF1 is probably involved in DNA binding, and loop L3 and helices α2 and α3 of one MHF1 subunit interact with those of the other to form two heterotetramer interfaces. Further genetic data demonstrate that the heterotetramer assembly is essential for the function of the complex in DNA repair. These results provide, to the best of our knowledge, new mechanistic insights into the function of the MHF complex.
GO:0003677
DNA binding
GO:0006281
DNA repair
GO:0071821
FANCM-MHF complex
Chains C and D were removed as chains A and B represent the biologically relevant dimer.
2
2
Histone-like interactions
Histone-like complexes
A
Uncharacterized protein YOL086W-A
Saccharomyces cerevisiae
MNDDEDRAQLKARLWIRVEERLQQVLSSEDIKYTPRFINSLLELAYLQLGEMGSDLQAFARHAGRGVVNKSDLMLYLRKQPDLQERVTQE
90
Q3E835
1
90
100%
UniRef90_Q3E835
1
90
secondary structure
helix
3
25
secondary structure
helix
35
51
secondary structure
helix
53
63
secondary structure
beta
68
69
secondary structure
helix
71
73
secondary structure
helix
75
78
secondary structure
helix
83
89
pfam
PF15630.3
CENP-S
8
83
B
Uncharacterized protein YDL160C-A
Saccharomyces cerevisiae
MLSKEALIKILSQNEGGNDMKIADEVVPMIQKYLDIFIDEAVLRSLQSHKDINGERGDKSPLELSHQDLERIVGLLLMDMLEHHHHHH
88
Q3E829
1
80
100%
UniRef90_Q3E829
1
80
secondary structure
helix
6
12
secondary structure
beta
23
24
secondary structure
helix
30
52
secondary structure
helix
64
64
secondary structure
helix
69
77
pfam
PF09415.7
CENP-X
4
80
Centromere proteins S and X (CENP-S and CENP-X), also called MHF1 and MHF2 form histone-like heterodimers (MHF complex, PMID:20347428). These dimers further associate with heterodimers formed by CENP-T and CENP-W and these tetrameric structures share a high degree of similarity with canonical histone multimers within the nucleosome (PMID:22304917). CENP-T-W-S-X tetramers - similarly to nucleosomes formed by histones - are able to bind and supercoil DNA (PMID:24234442). Apart from some structural differences leading to different functions (e.g. CENP-T-W-S-X tetramers show a preference for branched DNA as opposed to nucleosomes, PMID:24390579), both the overall and the underlying basic structures of nucleosomes and CENP-T-W-S-X tetramers are essentially the same with both CENP-S/CENP-X and CENP-T/W dimers forming structures nearly identical to that of histone dimers (PMID:20347428 and PMID:19070575). Histone dimerization has been experimentally characterized to be coupled to the structure formation of both interacting partners (PMID:12779337); this synergistic folding has been shown separately for various histone dimers (PMID:15588829, PMID:15096635). Histones containing various types of monomeric subunits can exhibit varying stability and folding kinetics; however, independent of composition and folding kinetics, all histones appear to fold in a cooperative fashion that is coupled to binding (PMID:11669650).
MF2210009
CENP-T/CENP-W dimer (Gallus gallus)
3b0c
X-ray
2.20
heterodimer
Gallus gallus
22304917
Nishino T, Takeuchi K, Gascoigne KE, Suzuki A, Hori T, Oyama T, Morikawa K, Cheeseman IM, Fukagawa T
CENP-T-W-S-X forms a unique centromeric chromatin structure with a histone-like fold.
Cell
2012
3
148
487-501
The multiprotein kinetochore complex must assemble at a specific site on each chromosome to achieve accurate chromosome segregation. Defining the nature of the DNA-protein interactions that specify the position of the kinetochore and provide a scaffold for kinetochore formation remain key goals. Here, we demonstrate that the centromeric histone-fold-containing CENP-T-W and CENP-S-X complexes coassemble to form a stable CENP-T-W-S-X heterotetramer. High-resolution structural analysis of the individual complexes and the heterotetramer reveals similarity to other histone fold-containing complexes including canonical histones within a nucleosome. The CENP-T-W-S-X heterotetramer binds to and supercoils DNA. Mutants designed to compromise heterotetramerization or the DNA-protein contacts around the heterotetramer strongly reduce the DNA binding and supercoiling activities in vitro and compromise kinetochore assembly in vivo. These data suggest that the CENP-T-W-S-X complex forms a unique nucleosome-like structure to generate contacts with DNA, extending the "histone code" beyond canonical nucleosome proteins.
GO:0003677
DNA binding
GO:0046982
protein heterodimerization activity
GO:0007059
chromosome segregation
GO:0051382
kinetochore assembly
GO:0051301
cell division
GO:0007067
mitotic nuclear division
GO:0005634
nucleus
GO:0000777
condensed chromosome kinetochore
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
2
Histone-like interactions
Histone-like complexes
T
Centromere protein T
Gallus gallus
GSTREPEIASSLIKQIFSHYVKTPVTRDAYKIVEKCSERYFKQISSDLEAYSQHAGRKTVEMADVELLMRRQGLVTDKMPLHVLVERHLPLEYRKLLIPIAVSGNKVIPCK
111
F1NPG5
529
639
17.4%
UniRef90_F1NPG5
531
639
secondary structure
helix
539
549
secondary structure
beta
553
553
secondary structure
helix
555
582
secondary structure
beta
587
588
secondary structure
helix
590
599
secondary structure
beta
604
604
secondary structure
beta
607
607
secondary structure
helix
609
616
secondary structure
helix
619
625
pfam
PF15511.3
CENP-T_C
529
631
W
Centromere protein W
Gallus gallus
GRRTVPRGTLRKIIKKHKPHLRLAANTDLLVHLSFLLFLHRLAEEARTNAFENKSKIIKPEHTIAAAKVILKKSRG
76
P0DJH6
2
76
98.7%
UniRef90_P0DJH6
2
76
secondary structure
helix
7
17
secondary structure
beta
22
23
secondary structure
helix
27
53
secondary structure
beta
58
58
secondary structure
helix
60
74
pfam
PF15510.3
CENP-W
1
76
Centromere proteins T and W (CENP-T and CENP-W) form histone-like heterodimers (PMID:19070575). These dimers further associate with heterodimers formed by CENP-S and CENP-X and these tetrameric structures share a high degree of similarity with canonical histone multimers within the nucleosome (PMID:22304917). CENP-T-W-S-X tetramers - similarly to nucleosomes formed by histones - are able to bind and supercoil DNA (PMID:24234442). Apart from some structural differences leading to different functions (e.g. CENP-T-W-S-X tetramers show a preference for branched DNA as opposed to nucleosomes, PMID:24390579), both the overall and the underlying basic structures of nucleosomes and CENP-T-W-S-X tetramers are essentially the same with both CENP-S/CENP-X and CENP-T/W dimers forming structures nearly identical to that of histone dimers (PMID:20347428 and PMID:19070575). Histone dimerization has been experimentally characterized to be coupled to the structure formation of both interacting partners (PMID:12779337); this synergistic folding has been shown separately for various histone dimers (PMID:15588829, PMID:15096635). Histones containing various types of monomeric subunits can exhibit varying stability and folding kinetics; however, independent of composition and folding kinetics, all histones appear to fold in a cooperative fashion that is coupled to binding (PMID:11669650).
3b0d
3vh5
3vh6
MF4110008
Oligomerization domain of Drosophila melanogaster p53
2rp4
NMR
homotetramer (dimer of dimers)
Drosophila melanogaster
17581633
Ou HD, Löhr F, Vogel V, Mäntele W, Dötsch V
Structural evolution of C-terminal domains in the p53 family.
EMBO J.
2007
14
26
3463-73
The tetrameric state of p53, p63, and p73 has been considered one of the hallmarks of this protein family. While the DNA binding domain (DBD) is highly conserved among vertebrates and invertebrates, sequences C-terminal to the DBD are highly divergent. In particular, the oligomerization domain (OD) of the p53 forms of the model organisms Caenorhabditis elegans and Drosophila cannot be identified by sequence analysis. Here, we present the solution structures of their ODs and show that they both differ significantly from each other as well as from human p53. CEP-1 contains a composite domain of an OD and a sterile alpha motif (SAM) domain, and forms dimers instead of tetramers. The Dmp53 structure is characterized by an additional N-terminal beta-strand and a C-terminal helix. Truncation analysis in both domains reveals that the additional structural elements are necessary to stabilize the structure of the OD, suggesting a new function for the SAM domain. Furthermore, these structures show a potential path of evolution from an ancestral dimeric form over a tetrameric form, with additional stabilization elements, to the tetramerization domain of mammalian p53.
GO:0003700
transcription factor activity, sequence-specific DNA binding
GO:0001097
TFIIH-class transcription factor binding
GO:0031624
ubiquitin conjugating enzyme binding
GO:0001047
core promoter binding
GO:0000976
transcription regulatory region sequence-specific DNA binding
GO:0031625
ubiquitin protein ligase binding
GO:0060785
regulation of apoptosis involved in tissue homeostasis
GO:0035234
ectopic germ cell programmed cell death
GO:2000685
positive regulation of cellular response to X-ray
GO:0006282
regulation of DNA repair
GO:0007131
reciprocal meiotic recombination
GO:0006919
activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0046533
negative regulation of photoreceptor cell differentiation
GO:0042127
regulation of cell proliferation
GO:0043568
positive regulation of insulin-like growth factor receptor signaling pathway
GO:1990248
regulation of transcription from RNA polymerase II promoter in response to DNA damage
GO:0042992
negative regulation of transcription factor import into nucleus
GO:0071480
cellular response to gamma radiation
GO:0043553
negative regulation of phosphatidylinositol 3-kinase activity
GO:0009411
response to UV
GO:0040015
negative regulation of multicellular organism growth
GO:0030330
DNA damage response, signal transduction by p53 class mediator
GO:0007405
neuroblast proliferation
GO:0048477
oogenesis
GO:0014016
neuroblast differentiation
GO:0042771
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:0009267
cellular response to starvation
GO:0045944
positive regulation of transcription from RNA polymerase II promoter
GO:0040010
positive regulation of growth rate
GO:0016239
positive regulation of macroautophagy
GO:0090278
negative regulation of peptide hormone secretion
GO:0046620
regulation of organ growth
GO:0045787
positive regulation of cell cycle
GO:0040018
positive regulation of multicellular organism growth
GO:0008340
determination of adult lifespan
GO:0042246
tissue regeneration
GO:0005634
nucleus
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
1
Other
p53 tetramerization
A
GH11591p
Drosophila melanogaster
GPLGSDDSAAEWNVSRTPDGDYRLAITCPNKEWLLQSIEGMIKEAAAEVLRNPNQENLRRHANKLLSLKKRAYELP
76
Q9N6D8
310
385
19.7%
UniRef90_Q9N6D8
315
385
secondary structure
beta
322
324
secondary structure
beta
330
337
secondary structure
helix
340
360
secondary structure
helix
365
383
pfam
PF11619.5
P53_C
319
385
B
GH11591p
Drosophila melanogaster
GPLGSDDSAAEWNVSRTPDGDYRLAITCPNKEWLLQSIEGMIKEAAAEVLRNPNQENLRRHANKLLSLKKRAYELP
76
Q9N6D8
310
385
19.7%
UniRef90_Q9N6D8
315
385
secondary structure
beta
322
325
secondary structure
beta
331
337
secondary structure
helix
340
360
secondary structure
helix
365
383
pfam
PF11619.5
P53_C
319
385
C
GH11591p
Drosophila melanogaster
GPLGSDDSAAEWNVSRTPDGDYRLAITCPNKEWLLQSIEGMIKEAAAEVLRNPNQENLRRHANKLLSLKKRAYELP
76
Q9N6D8
310
385
19.7%
UniRef90_Q9N6D8
315
385
secondary structure
beta
322
324
secondary structure
beta
331
337
secondary structure
helix
340
360
secondary structure
helix
365
383
pfam
PF11619.5
P53_C
319
385
D
GH11591p
Drosophila melanogaster
GPLGSDDSAAEWNVSRTPDGDYRLAITCPNKEWLLQSIEGMIKEAAAEVLRNPNQENLRRHANKLLSLKKRAYELP
76
Q9N6D8
310
385
19.7%
UniRef90_Q9N6D8
315
385
secondary structure
beta
322
326
secondary structure
beta
330
337
secondary structure
helix
340
360
secondary structure
helix
365
383
pfam
PF11619.5
P53_C
319
385
While the C-terminal region of p53 from humans and D. melanogaster do not share a high degree of sequential identity, they are structurally and functionally similar (PMID:10778859). The oligomerization domain (OD) of D. melanogaster p53 (Dmp53) includes the structural elements of that of human p53 exhibiting a four-helix bundle structure bound by hydrophobic and electrostatic interactions (PMID:8023159). Human p53 tetramer is formed as a dimer of dimers and follows a two state folding and binding process, demonstrated in several chemical and thermal denaturation/refolding experiments (PMID:9582268, PMID:18410249, PMID:19913028). The main difference between the two p53 variants are the additional structural elements in Dmp53 OD which comprise an additional helix and a beta-strand. The deletion of these structural elements destabilize the oligomer hinting at a suboptimal binding of the core structural elements compared to the human counterpart (PMID:17581633).
MF2210010
Bulb-type mannose-binding lectin (Allium sativum)
1kj1
X-ray
2.20
heterodimer
Allium sativum
11856826
Ramachandraiah G, Chandra NR, Surolia A, Vijayan M
Re-refinement using reprocessed data to improve the quality of the structure: a case study involving garlic lectin.
Acta Crystallogr. D Biol. Crystallogr.
2002
Pt 3
58
414-20
The structure of dimeric garlic lectin was previously determined to an effective resolution of 2.8A using X-ray intensity data processed by the XDS package and refined using X-PLOR [Chandra et al. (1999), J. Mol. Biol. 285, 1157--1168]. Repeated attempts to grow better crystals with a view to improving the definition of the structure did not succeed. The available raw data were then reprocessed using DENZO. The structure was re-refined with both X-PLOR and CNS separately using the reprocessed data, which extended to a resolution of 2.2A. These two sets of refinements and the two sets using the XDS-processed data afforded an opportunity to compare the performance of different data-processing and refinement packages when dealing with data from weakly diffracting crystals. The best results were obtained when CNS was employed for refinement using data processed by DENZO. The quality and the resolution of the map and the definition of the structure improved substantially. In particular, the amino-acid residues at the variable locations in the sequence, and hence the isolectins, could be identified with a high degree of confidence. It could be established that the crystal asymmetric unit contains two identical heterodimers. The new refined structure also provided a better definition of other finer structural details.
GO:0030246
carbohydrate binding
Chains P and Q were removed as chains A and D represent the biologically relevant dimer.
2
2
Bulb-type lectin domain
Heterodimeric lectin
A
I lectin (Precursor)
Allium sativum
RNLLTNGEGLYAGQSLDVEPYHFIMQEDCNLVLYDHSTSVWASNTGILGKKGCKAVLQSDGNFVVYDAEGRSLWASHSVRGNGNYVLVLQEDGNVVIYGSDIWSTGTYK
109
Q38789
177
285
36%
UniRef90_Q38789
177
285
secondary structure
beta
179
181
secondary structure
beta
185
187
secondary structure
beta
191
194
secondary structure
beta
197
201
secondary structure
beta
207
211
secondary structure
beta
214
218
secondary structure
beta
230
233
secondary structure
beta
239
242
secondary structure
beta
248
251
secondary structure
beta
262
265
secondary structure
beta
271
274
secondary structure
beta
277
280
pfam
PF01453.21
B_lectin
185
258
D
II lectin (Precursor)
Allium sativum
RNILMNDEGLYAGQSLDVEPYHLIMQEDCNLVLYDHSTAVWTTNTDIPGKKGCKAVLQSDGNFVVYDAEGRSLWASHSVRGNGNYVLVLQEDGNVVIYGSDIWSTNTYK
109
Q38783
29
137
70.3%
UniRef90_Q38784
18
126
secondary structure
beta
31
33
secondary structure
beta
37
39
secondary structure
beta
43
46
secondary structure
beta
49
53
secondary structure
beta
59
63
secondary structure
beta
66
70
secondary structure
beta
82
85
secondary structure
beta
91
94
secondary structure
beta
100
103
secondary structure
beta
113
117
secondary structure
beta
123
127
secondary structure
beta
129
132
pfam
PF01453.21
B_lectin
29
111
The association between the two subunits of mannose-binding lectin from garlic bulbs was shown to be highly reversible and can be defined as a two-state process in which the folded dimer is converted directly into the unfolded monomers (PMID:11401577).
1bwu
MF2110013
Bulb-type lectin (Allium sativum)
4h3o
X-ray
2.17
homodimer
Allium sativum
Kumar, S., Yamini, S., Kumar, J., Kaur, P., Singh, T.P., Dey, S.
Crystal structure of a new form of lectin from Allium sativum at 2.17 A resolution
To be published
-
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Bulb-type lectin domain
Homodimeric lectin
A
Lectin
Allium sativum
RNILDNNEGLYAGQSLDVEPYHFIMQDDCNLVLYDHSTSTWASNTEIGGKSGCSAVLQSDGNFVVYDSSGRSLWASHSTRGSGNYILILQDDGNVIIYGSDIWST
105
K4DIE9
1
105
100%
UniRef90_K4DIE9
1
105
secondary structure
beta
3
4
secondary structure
beta
8
10
secondary structure
beta
15
18
secondary structure
beta
21
25
secondary structure
beta
31
35
secondary structure
beta
38
42
secondary structure
beta
54
57
secondary structure
beta
63
66
secondary structure
beta
72
75
secondary structure
beta
85
89
secondary structure
beta
95
99
secondary structure
beta
101
104
pfam
PF01453.21
B_lectin
9
83
B
Lectin
Allium sativum
RNILDNNEGLYAGQSLDVEPYHFIMQDDCNLVLYDHSTSTWASNTEIGGKSGCSAVLQSDGNFVVYDSSGRSLWASHSTRGSGNYILILQDDGNVIIYGSDIWST
105
K4DIE9
1
105
100%
UniRef90_K4DIE9
1
105
secondary structure
beta
3
4
secondary structure
beta
8
10
secondary structure
beta
15
18
secondary structure
beta
21
25
secondary structure
beta
31
35
secondary structure
beta
38
42
secondary structure
beta
54
57
secondary structure
beta
63
66
secondary structure
beta
72
75
secondary structure
beta
86
89
secondary structure
beta
95
98
secondary structure
beta
101
104
pfam
PF01453.21
B_lectin
9
83
A very closely homologous lectin of the same type from the same organism sharing a high degree of sequence and structural similarity has been shown to follow a two-state folding process (PMID:11401577).
MF2110014
Mannose-binding lectin (Narcissus pseudonarcissus)
3dzw
X-ray
1.70
homodimer
Galanthus nivalis
Rizkallah, P.J., Ozbey, S., Sauerborn, M.K.
Structure of Narcissus pseudonarcissus lectin complex with Mannobiose at 1.7 A resolution, form II
To be published
-
GO:0005537
mannose binding
GO:0005576
extracellular region
Chain C was generated from chain A using the biomatrix described in the original PDB file. Chain B was removed as chains A and C represent the biologically relevant dimer.
2
1
Bulb-type lectin domain
Homodimeric lectin
A
Mannose-specific lectin
Galanthus nivalis
DNILYSGETLSPGEFLNNGRYVFIMQEDCNLVLYDVDKPIWATNTGGLDRRCHLSMQSDGNLVVYSPRNNPIWASNTGGENGNYVCVLQKDRNVVIYGTARWATGTNIH
109
P30617
24
130
68.2%
UniRef90_P30617
24
130
secondary structure
beta
26
28
secondary structure
beta
31
33
secondary structure
beta
38
41
secondary structure
beta
44
48
secondary structure
beta
54
58
secondary structure
beta
61
65
secondary structure
beta
76
79
secondary structure
beta
85
88
secondary structure
beta
94
97
secondary structure
beta
107
111
secondary structure
beta
117
121
secondary structure
beta
123
126
pfam
PF01453.21
B_lectin
24
128
C
Mannose-specific lectin
Galanthus nivalis
DNILYSGETLSPGEFLNNGRYVFIMQEDCNLVLYDVDKPIWATNTGGLDRRCHLSMQSDGNLVVYSPRNNPIWASNTGGENGNYVCVLQKDRNVVIYGTARWATGTNIH
109
P30617
24
130
68.2%
UniRef90_P30617
24
130
secondary structure
beta
26
28
secondary structure
beta
31
33
secondary structure
beta
38
41
secondary structure
beta
44
48
secondary structure
beta
54
58
secondary structure
beta
61
65
secondary structure
beta
76
79
secondary structure
beta
85
88
secondary structure
beta
94
97
secondary structure
beta
107
111
secondary structure
beta
117
121
secondary structure
beta
123
126
pfam
PF01453.21
B_lectin
24
128
A closely homologous lectin of the same type sharing a high degree of sequence and structural similarity has been shown to follow a two-state folding process (PMID:11401577).
1jpc
1msa
1niv
1npl
MF2110015
Mannose-binding lectin (Polygonatum cyrtonema)
3a0e
X-ray
2.00
homodimer
Polygonatum cyrtonema
20546901
Ding J, Bao J, Zhu D, Zhang Y, Wang DC
Crystal structures of a novel anti-HIV mannose-binding lectin from Polygonatum cyrtonema Hua with unique ligand-binding property and super-structure.
J. Struct. Biol.
2010
3
171
309-17
Polygonatum cyrtonema lectin (PCL) is a novel anti-HIV mannose-binding lectin from Galanthus nivalis agglutinin (GNA)-related lectin family. Crystal structures of ligand-free PCL and its complexes with monomannoside and alpha1-3 dimannoside have been determined. The ligand-free PCL is dimeric, with both subunits adopt the beta-prism II fold. PCL subunit binds mannose using a potential bivalent mode instead of the usual trivalent mode, in which carbohydrate-binding site (CBS) I and CBS III adopt the conserved mannose-binding motif of QXDXNXVXY (X is one of any amino acid residues) as observed in other structurally characterized GNA-related lectins, while CBS II adopts a modified motif with residues Gln58 and Asp60, which are critical for mannose-binding, substituted by His58 and Asn60, respectively. As a result, CBS II is unfit for mannose-binding. In the mannoside complexes, ligand-bindings only occur at CBS I which provides the specificity for alpha1-3 dimannoside. CBS II and CBS III are cooperatively occupied by a well-ordered sulfate ion, through which the individual dimers are cross-linked to form a unique super-structure of 3(2) helical lattice. Surveying the sequences of GNA-related lectins revealed that the modified binding motif of CBS II is widely distributed in the Liliaceae family as an intrinsic structural element. There is evidence that other GNA-related lectins will also adopt the similar super-structure as PCL. Thus PCL structure, unique in ligand-binding mode, may represent a novel type of structure of GNA-related lectins. Comparative analyses indicated that the dimer-based super-structure may play a primary role in the anti-HIV property of PCL.
GO:0030246
carbohydrate binding
Chain B was generated from chain A using the biomatrix described in the original PDB file.
2
1
Bulb-type lectin domain
Homodimeric lectin
A
Mannose/sialic acid-binding lectin
Polygonatum cyrtonema
VNSLSSPNSLFTGHSLEVGPSYRLIMQGDCNFVLYDSGKPVWASNTGGLGSGCRLTLHNNGNLVIYDQSNRVIWQTKTNGKEDHYVLVLQQDRNVVIYGPVVWATGSGPA
110
Q8L568
29
138
68.8%
UniRef90_Q8L568
29
138
secondary structure
beta
31
33
secondary structure
beta
37
38
secondary structure
beta
43
46
secondary structure
beta
50
54
secondary structure
beta
60
64
secondary structure
beta
67
71
secondary structure
beta
82
85
secondary structure
beta
91
94
secondary structure
beta
100
103
secondary structure
beta
114
117
secondary structure
beta
123
126
secondary structure
beta
129
132
pfam
PF01453.21
B_lectin
36
134
B
Mannose/sialic acid-binding lectin
Polygonatum cyrtonema
VNSLSSPNSLFTGHSLEVGPSYRLIMQGDCNFVLYDSGKPVWASNTGGLGSGCRLTLHNNGNLVIYDQSNRVIWQTKTNGKEDHYVLVLQQDRNVVIYGPVVWATGSGPA
110
Q8L568
29
138
68.8%
UniRef90_Q8L568
29
138
secondary structure
beta
31
33
secondary structure
beta
37
38
secondary structure
beta
43
46
secondary structure
beta
50
54
secondary structure
beta
60
64
secondary structure
beta
67
71
secondary structure
beta
82
85
secondary structure
beta
91
94
secondary structure
beta
100
103
secondary structure
beta
114
117
secondary structure
beta
123
126
secondary structure
beta
129
132
pfam
PF01453.21
B_lectin
36
134
A closely homologous lectin of the same type sharing a high degree of sequence and structural similarity has been shown to follow a two-state folding process (PMID:11401577).
3a0c
3a0d
MF2210011
Tuber agglutinin (Colocasia esculenta)
5d5g
X-ray
1.74
heterodimer
Colocasia esculenta
Biswas, H., Chattopadhyaya, R.
Crystal Structure of Colocasia esculenta tuber agglutinin : quarternary interactions and conformational stability
To be published
-
Chains C and D were removed as chains A and B represent the biologically relevant dimer.
2
2
Bulb-type lectin domain
Heterodimeric lectin
A
Tuber agglutinin
Colocasia esculenta
LGTNYLLSGQTLDREGHLKNGDFDLVMQDDCNLVLYNGNWQSNTANKGRDCKLTLTDYGELVIKNGDGSTVWRSRAQSVKGNYAAVVHPDGRLVVFGPSVFKIDPWVPG
109
R9RL27
24
132
41.3%
UniRef90_R9RL27
24
132
secondary structure
beta
25
25
secondary structure
beta
28
30
secondary structure
beta
34
35
secondary structure
beta
39
43
secondary structure
beta
46
50
secondary structure
beta
56
59
secondary structure
beta
63
64
secondary structure
beta
75
78
secondary structure
beta
84
87
secondary structure
beta
93
96
secondary structure
beta
107
111
secondary structure
beta
115
119
secondary structure
beta
122
126
pfam
PF01453.21
B_lectin
26
116
B
Tuber agglutinin
Colocasia esculenta
NIPFTNNLLFSGQVLYGDGRLTAKSHQLVMQGDCNLVLYGGKYGWQSNTHGNGEHCFLRLNHKGELIIKDDDFKTIWSSSSSSKHGDYVLILRDDGFAVIYGPAIWETSPQ
111
R9RL27
140
250
42%
UniRef90_R9RL27
140
250
secondary structure
beta
147
149
secondary structure
beta
153
155
secondary structure
beta
158
162
secondary structure
beta
165
169
secondary structure
beta
175
178
secondary structure
beta
184
185
secondary structure
beta
196
199
secondary structure
beta
205
208
secondary structure
beta
214
217
secondary structure
beta
228
231
secondary structure
beta
237
240
secondary structure
beta
243
246
pfam
PF01453.21
B_lectin
145
248
A closely homologous lectin of the same type sharing a high degree of sequence and structural similarity has been shown to follow a two-state folding process (PMID:11401577).
5d9z
3r0e
5t1x
5t20
MF2210012
Neoculin heterodimer (Molineria latifolia)
2d04
X-ray
2.76
heterodimer
Molineria latifolia
16616933
Shimizu-Ibuka A, Morita Y, Terada T, Asakura T, Nakajima K, Iwata S, Misaka T, Sorimachi H, Arai S, Abe K
Crystal structure of neoculin: insights into its sweetness and taste-modifying activity.
J. Mol. Biol.
2006
1
359
148-58
Although the majority of sweet compounds are of low molecular mass, several proteins are known to elicit sweet taste responses in humans. The fruit of Curculigo latifolia contains a heterodimeric protein, neoculin, which has both sweetness and a taste-modifying activity that converts sourness to sweetness. Here, we report the crystal structure of neoculin at 2.76A resolution. This is the first well-defined tertiary structure of a taste-modifying protein of this kind. The overall structure is quite similar to those of monocot mannose-binding lectins. However, crucial topological differences are observed in the C-terminal regions of both subunits. In both subunits of neoculin, the C-terminal tails turn up to form loops fixed by inter-subunit disulfide bonds that are not observed in the lectins. Indeed, the corresponding regions of the lectins stretch straight over the surface of another subunit. Such a C-terminal structural feature as is observed in neoculin results in a decrease in subunit-subunit interactions. Moreover, distribution of electrostatic potential on the surface of neoculin is unique and significantly different from those of the lectins, particularly in the basic subunit (NBS). We have found that there is a large cluster composed of six basic residues on the surface of NBS, and speculate that it might be involved in the elicitation of sweetness and/or taste-modifying activity of neoculin. Molecular dynamics simulation based on the crystallography results suggests that neoculin may adopt a widely "open" conformation at acidic pH, while unprotonated neoculin at neutral pH is in a "closed" conformation. Based on these simulations and the generation of a docking model between neoculin and the sweet-taste receptor, T1R2-T1R3, we propose the hypothesis that neoculin is in dynamic equilibrium between open and closed states, and that the addition of an acid shifts the equilibrium to the open state, allowing ligand-receptor interaction.
GO:0030246
carbohydrate binding
Chains C, D, E, F, G and H were removed as chains A and B represent the biologically relevant dimer.
2
2
Bulb-type lectin domain
Heterodimeric lectin
A
Curculin-2
Molineria latifolia
DSVLLSGQTLYAGHSLTSGSYTLTIQNNCNLVKYQHGRQIWASDTDGQGSQCRLTLRSDGNLIIYDDNNMVVWGSDCWGNNGTYALVLQQDGLFVIYGPVLWPLGLNGCRSLN
113
Q6F495
23
135
71.5%
UniRef90_Q6F495
23
135
secondary structure
beta
25
27
secondary structure
beta
31
32
secondary structure
beta
36
40
secondary structure
beta
43
47
secondary structure
beta
53
57
secondary structure
beta
60
64
secondary structure
beta
75
78
secondary structure
beta
84
87
secondary structure
beta
93
95
secondary structure
beta
107
110
secondary structure
beta
116
119
secondary structure
beta
122
122
secondary structure
beta
125
125
secondary structure
beta
130
130
pfam
PF01453.21
B_lectin
23
103
B
Curculin-1
Molineria latifolia
DNVLLSGQTLHADHSLQAGAYTLTIQNKCNLVKYQNGRQIWASNTDRRGSGCRLTLLSDGNLVIYDHNNNDVWGSACWGDNGKYALVLQKDGRFVIYGPVLWSLGPNGCRRVNG
114
P19667
23
136
72.2%
UniRef90_P19667
23
136
secondary structure
beta
25
27
secondary structure
beta
31
32
secondary structure
beta
37
40
secondary structure
beta
43
47
secondary structure
beta
53
57
secondary structure
beta
60
64
secondary structure
beta
75
78
secondary structure
beta
84
87
secondary structure
beta
93
96
secondary structure
beta
107
110
secondary structure
beta
116
119
secondary structure
beta
122
124
secondary structure
beta
131
131
pfam
PF01453.21
B_lectin
23
101
A closely homologous protein (bulb-type lectin) sharing a high degree of sequence and structural similarity has been shown to follow a two-state folding process (PMID:11401577).
2dpf
MF2210013
Mannose-binding lectin (Crocus vernus)
3mez
X-ray
1.94
heterodimer
Crocus vernus
Akrem, A.
X-ray structural analysis of a mannose specific lectin from dutch crocus (crocus vernus)
To be published
-
GO:0005537
mannose binding
Chains C and D were removed as chains A and B represent the biologically relevant dimer.
2
2
Bulb-type lectin domain
Heterodimeric lectin
A
Mannose-specific lectin 3
Crocus vernus
DNNVLLTGDVIHTDNQLSYESAAFVMQGDCNLVLYNEAGGFQSNTHGRGVDCTLRLNNRGQLEIHSANSNTPVWVYPRSVNTVRGNYAATLGPDQHVTIYGPAIWSTPAAA
111
P86626
1
111
49.6%
UniRef90_P86626
1
111
secondary structure
beta
4
6
secondary structure
beta
10
11
secondary structure
beta
16
19
secondary structure
beta
22
26
secondary structure
beta
32
35
secondary structure
beta
41
42
secondary structure
beta
53
56
secondary structure
beta
62
65
secondary structure
beta
74
76
secondary structure
beta
88
91
secondary structure
beta
97
100
secondary structure
beta
103
106
pfam
PF01453.21
B_lectin
2
108
B
Mannose-specific lectin 3
Crocus vernus
NIPRVRNVLFSSQVMYDNAQLATRDYSLVMRDDCNLVLTKGSKTNIVWESGTSGRGQHCFMRLGHSGELDITDDRLNTVFVSNTVGQEGDYVLILQINGQAVVYGPAVWSTAA
113
P86626
112
224
50.4%
UniRef90_P86626
112
224
secondary structure
beta
119
121
secondary structure
beta
125
127
secondary structure
beta
131
134
secondary structure
beta
137
141
secondary structure
beta
147
151
secondary structure
beta
156
160
secondary structure
beta
171
174
secondary structure
beta
180
183
secondary structure
beta
189
192
secondary structure
beta
203
206
secondary structure
beta
212
215
secondary structure
beta
218
221
pfam
PF01453.21
B_lectin
117
223
A closely homologous protein (bulb-type lectin) sharing a high degree of sequence and structural similarity has been shown to follow a two-state folding process (PMID:11401577).
MF2100009
Basic HLH/leucine zipper domain of Max
1r05
NMR
homodimer
Homo sapiens
15342239
Sauvé S, Tremblay L, Lavigne P
The NMR solution structure of a mutant of the Max b/HLH/LZ free of DNA: insights into the specific and reversible DNA binding mechanism of dimeric transcription factors.
J. Mol. Biol.
2004
3
342
813-32
Basic region-helix1-loop-helix2-leucine zipper (b/H(1)LH(2)/LZ) transcription factors bind specific DNA sequence in their target gene promoters as dimers. Max, a b/H(1)LH(2)/LZ transcription factor, is the obligate heterodimeric partner of the related b/H(1)LH(2)/LZ proteins of the Myc and Mad families. These heterodimers specifically bind E-box DNA sequence (CACGTG) to activate (e.g. c-Myc/Max) and repress (e.g. Mad1/Max) transcription. Max can also homodimerize and bind E-box sequences in c-Myc target gene promoters. While the X-ray structure of the Max b/H(1)LH(2)/LZ/DNA complex and that of others have been reported, the precise sequence of events leading to the reversible and specific binding of these important transcription factors is still largely unknown. In order to provide insights into the DNA binding mechanism, we have solved the NMR solution structure of a covalently homodimerized version of a Max b/H(1)LH(2)/LZ protein with two stabilizing mutations in the LZ, and characterized its backbone dynamics from (15)N spin-relaxation measurements in the absence of DNA. Apart from minor differences in the pitch of the LZ, possibly resulting from the mutations in the construct, we observe that the packing of the helices in the H(1)LH(2) domain is almost identical to that of the two crystal structures, indicating that no important conformational change in these helices occurs upon DNA binding. Conversely to the crystal structures of the DNA complexes, the first 14 residues of the basic region are found to be mostly unfolded while the loop is observed to be flexible. This indicates that these domains undergo conformational changes upon DNA binding. On the other hand, we find the last four residues of the basic region form a persistent helical turn contiguous to H(1). In addition, we provide evidence of the existence of internal motions in the backbone of H(1) that are of larger amplitude and longer time-scale (nanoseconds) than the ones in the H(2) and LZ domain. Most interestingly, we note that conformers in the ensemble of calculated structures have highly conserved basic residues (located in the persistent helical turn of the basic region and in the loop) known to be important for specific binding in a conformation that matches that of the DNA-bound state. These partially prefolded conformers can directly fit into the major groove of DNA and as such are proposed to lie on the pathway leading to the reversible and specific DNA binding. In these conformers, the conserved basic side-chains form a cluster that elevates the local electrostatic potential and could provide the necessary driving force for the generation of the internal motions localized in the H(1) and therefore link structural determinants with the DNA binding function. Overall, our results suggests that the Max homodimeric b/H(1)LH(2)/LZ can rapidly and preferentially bind DNA sequence through transient and partially prefolded states and subsequently, adopt the fully helical bound state in a DNA-assisted mechanism or induced-fit.
GO:0003713
transcription coactivator activity
GO:0042803
protein homodimerization activity
GO:0000978
RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0046982
protein heterodimerization activity
GO:0032403
protein complex binding
GO:0000983
transcription factor activity, RNA polymerase II core promoter sequence-specific
GO:0006366
transcription from RNA polymerase II promoter
GO:0006357
regulation of transcription from RNA polymerase II promoter
GO:0048678
response to axon injury
GO:0006461
protein complex assembly
GO:0009267
cellular response to starvation
GO:0060041
retina development in camera-type eye
GO:0032868
response to insulin
GO:0010629
negative regulation of gene expression
GO:0071375
cellular response to peptide hormone stimulus
GO:0051402
neuron apoptotic process
GO:0030425
dendrite
GO:0016605
PML body
GO:0071339
MLL1 complex
GO:0005737
cytoplasm
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Other
Basic helix-loop-helix (bHLH)
A
Protein max
Homo sapiens
MADKRAHHNALERKRRDHIKDSFHSLRDSVPSLQGEKASRAQILDKATEYIQYMRRKVHTLQQDIDDLKRQNALLEQQVRALEGSGC
87
P61244
21
107
54.4%
UniRef90_P61244
22
103
secondary structure
helix
38
49
secondary structure
helix
53
56
secondary structure
helix
62
102
pfam
PF00010.23
HLH
24
75
B
Protein max
Homo sapiens
MADKRAHHNALERKRRDHIKDSFHSLRDSVPSLQGEKASRAQILDKATEYIQYMRRKVHTLQQDIDDLKRQNALLEQQVRALEGSGC
87
P61244
21
107
54.4%
UniRef90_P61244
22
103
secondary structure
helix
38
49
secondary structure
helix
53
56
secondary structure
helix
62
102
pfam
PF00010.23
HLH
24
75
Monomeric elements of basic helix-loop-helix domains were shown to be natively unfolded with a pH-dependent premolten globule conformation, as shown by several spectroscopic techniques (NMR, fluorescence, FTIR, and circular dichroism) (PMID:20102160, PMID:8303294).
A
The 1-110 region described in DisProt entry DP00084 covers 100% of the sequence present in the structure.
B
The 1-110 region described in DisProt entry DP00084 covers 100% of the sequence present in the structure.
1nlw
1an2
1hlo
5eyo
MF2100010
Transcription factor HES-1 dimer
2mh3
NMR
homodimer
Homo sapiens
24403087
Popovic M, Wienk H, Coglievina M, Boelens R, Pongor S, Pintar A
The basic-helix-loop-helix region of the transcriptional repressor HES-1 is preorganized to bind DNA.
Proteins
2014
HES-1, one of the main downstream effectors in Notch signaling, is a transcriptional repressor of the basic helix-loop-helix (bHLH) family. Using NMR methods, we have determined the structure and dynamics of a recombinant protein, H1H, which includes an N-terminal segment, b1, containing functionally important phosphorylation sites, the basic region b2, required for binding to DNA, and the helix-loop-helix domain (HLH). We show that a proline residue in the sequence divides the protein in two parts, a flexible and disordered N-terminal region including b1 and a structured, mainly helical region comprising b2 and the HLH domain. Binding of H1H to a dsDNA oligonucleotide was monitored through the chemical shift perturbation of backbone amide resonances, and showed that the interaction surface involves not only the b2 segment, but also several residues in the b1 and HLH regions. © Proteins 2014;. © 2014 Wiley Periodicals, Inc.
GO:0043565
sequence-specific DNA binding
GO:0042826
histone deacetylase binding
GO:0008134
transcription factor binding
GO:0071820
N-box binding
GO:0042803
protein homodimerization activity
GO:0051087
chaperone binding
GO:0001078
transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0035910
ascending aorta morphogenesis
GO:0021537
telencephalon development
GO:0045977
positive regulation of mitotic cell cycle, embryonic
GO:0031016
pancreas development
GO:0090162
establishment of epithelial cell polarity
GO:0007219
Notch signaling pathway
GO:2000978
negative regulation of forebrain neuron differentiation
GO:0097084
vascular smooth muscle cell development
GO:0061106
negative regulation of stomach neuroendocrine cell differentiation
GO:0072012
glomerulus vasculature development
GO:0060412
ventricular septum morphogenesis
GO:0030901
midbrain development
GO:0030324
lung development
GO:0048711
positive regulation of astrocyte differentiation
GO:0021984
adenohypophysis development
GO:0061626
pharyngeal arch artery morphogenesis
GO:2000737
negative regulation of stem cell differentiation
GO:2000227
negative regulation of pancreatic A cell differentiation
GO:0021557
oculomotor nerve development
GO:0042102
positive regulation of T cell proliferation
GO:0016477
cell migration
GO:0021861
forebrain radial glial cell differentiation
GO:0048715
negative regulation of oligodendrocyte differentiation
GO:0030513
positive regulation of BMP signaling pathway
GO:0003266
regulation of secondary heart field cardioblast proliferation
GO:0060253
negative regulation of glial cell proliferation
GO:0048538
thymus development
GO:0072050
S-shaped body morphogenesis
GO:0072049
comma-shaped body morphogenesis
GO:0006461
protein complex assembly
GO:0045608
negative regulation of auditory receptor cell differentiation
GO:0045598
regulation of fat cell differentiation
GO:0061009
common bile duct development
GO:0060716
labyrinthine layer blood vessel development
GO:0046331
lateral inhibition
GO:0048469
cell maturation
GO:0007224
smoothened signaling pathway
GO:0043388
positive regulation of DNA binding
GO:0061309
cardiac neural crest cell development involved in outflow tract morphogenesis
GO:0060122
inner ear receptor stereocilium organization
GO:0045747
positive regulation of Notch signaling pathway
GO:0007155
cell adhesion
GO:0035019
somatic stem cell population maintenance
GO:0048667
cell morphogenesis involved in neuron differentiation
GO:1903955
positive regulation of protein targeting to mitochondrion
GO:0042668
auditory receptor cell fate determination
GO:0050678
regulation of epithelial cell proliferation
GO:0042517
positive regulation of tyrosine phosphorylation of Stat3 protein
GO:0021575
hindbrain morphogenesis
GO:0006351
transcription, DNA-templated
GO:0072282
metanephric nephron tubule morphogenesis
GO:0003143
embryonic heart tube morphogenesis
GO:0001889
liver development
GO:0000122
negative regulation of transcription from RNA polymerase II promoter
GO:0090102
cochlea development
GO:0045944
positive regulation of transcription from RNA polymerase II promoter
GO:0021558
trochlear nerve development
GO:0072141
renal interstitial fibroblast development
GO:0097150
neuronal stem cell population maintenance
GO:0021555
midbrain-hindbrain boundary morphogenesis
GO:0060164
regulation of timing of neuron differentiation
GO:2000974
negative regulation of pro-B cell differentiation
GO:0060675
ureteric bud morphogenesis
GO:0007262
STAT protein import into nucleus
GO:0005737
cytoplasm
GO:0005654
nucleoplasm
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Other
Basic helix-loop-helix (bHLH)
A
Transcription factor HES-1
Homo sapiens
MKPKTASEHRKSSKPIMEKRRRARINESLSQLKTLILDALKKDSSRHSKLEKADILEMTVKHLRNLQRAQ
70
Q14469
26
95
25%
UniRef90_P35428
27
95
secondary structure
helix
40
65
secondary structure
helix
71
73
secondary structure
helix
77
93
pfam
PF00010.23
HLH
35
92
B
Transcription factor HES-1
Homo sapiens
MKPKTASEHRKSSKPIMEKRRRARINESLSQLKTLILDALKKDSSRHSKLEKADILEMTVKHLRNLQRAQ
70
Q14469
26
95
25%
UniRef90_P35428
27
95
secondary structure
helix
40
65
secondary structure
helix
77
93
pfam
PF00010.23
HLH
35
92
Monomeric elements of basic helix-loop-helix domains were shown to be natively unfolded with a pH-dependent premolten globule conformation, as shown by several spectroscopic techniques (NMR, fluorescence, FTIR, and circular dichroism) (PMID:20102160, PMID:8303294).
A
A close homologue sharing the same Pfam domain (PF00010.23) has been experimentally characterized as disordered in DisProt entries DP00084 and DP00672, and IDEAL entry IID00121.
B
A close homologue sharing the same Pfam domain (PF00010.23) has been experimentally characterized as disordered in DisProt entries DP00084 and DP00672, and IDEAL entry IID00121.
MF2100011
DNA-binding protein inhibitor ID-3
2lfh
NMR
homodimer
Homo sapiens
Eletsky, A., Wang, D., Kohan, E., Janjua, H., Acton, T.B., Xiao, R., Everett, J.K., Montelione, G.T., Szyperski, T.
Solution NMR Structure of the Helix-loop-Helix Domain of Human ID3 Protein, Northeast Structural Genomics Consortium Target HR3111A
To be published
-
GO:0019904
protein domain specific binding
GO:0046983
protein dimerization activity
GO:0008134
transcription factor binding
GO:1901707
leptomycin B binding
GO:0003700
transcription factor activity, sequence-specific DNA binding
GO:0003714
transcription corepressor activity
GO:0042476
odontogenesis
GO:0030903
notochord development
GO:0006275
regulation of DNA replication
GO:0030855
epithelial cell differentiation
GO:0009611
response to wounding
GO:0007417
central nervous system development
GO:0000122
negative regulation of transcription from RNA polymerase II promoter
GO:0006351
transcription, DNA-templated
GO:0007507
heart development
GO:0043433
negative regulation of sequence-specific DNA binding transcription factor activity
GO:0045668
negative regulation of osteoblast differentiation
GO:0001656
metanephros development
GO:0007623
circadian rhythm
GO:0030182
neuron differentiation
GO:0043065
positive regulation of apoptotic process
GO:0072750
cellular response to leptomycin B
GO:0051726
regulation of cell cycle
GO:0007517
muscle organ development
GO:0045662
negative regulation of myoblast differentiation
GO:0015630
microtubule cytoskeleton
GO:0005654
nucleoplasm
GO:0005737
cytoplasm
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Other
Basic helix-loop-helix (bHLH)
A
DNA-binding protein inhibitor ID-3
Homo sapiens
MGHHHHHHSHMGGGKGPAAEEPLSLLDDMNHCYSRLRELVPGVPRGTQLSQVEILQRVIDYILDLQVV
68
Q02535
27
83
47.9%
UniRef90_P41133
27
83
secondary structure
beta
34
34
secondary structure
helix
43
54
secondary structure
helix
66
81
pfam
PF00010.23
HLH
40
81
B
DNA-binding protein inhibitor ID-3
Homo sapiens
MGHHHHHHSHMGGGKGPAAEEPLSLLDDMNHCYSRLRELVPGVPRGTQLSQVEILQRVIDYILDLQVV
68
Q02535
27
83
47.9%
UniRef90_P41133
27
83
secondary structure
helix
43
53
secondary structure
beta
63
63
secondary structure
helix
66
81
pfam
PF00010.23
HLH
40
81
Monomeric elements of basic helix-loop-helix domains were shown to be natively unfolded with a pH-dependent premolten globule conformation, as shown by several spectroscopic techniques (NMR, fluorescence, FTIR, and circular dichroism) (PMID:20102160, PMID:8303294).
A
A close homologue sharing the same Pfam domain (PF00010.23) has been experimentally characterized as disordered in DisProt entries DP00084 and DP00672, and IDEAL entry IID00121.
B
A close homologue sharing the same Pfam domain (PF00010.23) has been experimentally characterized as disordered in DisProt entries DP00084 and DP00672, and IDEAL entry IID00121.
MF2120021
CesAB chaperone homodimer
2lhk
NMR
homodimer
Escherichia coli
22152477
Chen L, Balabanidou V, Remeta DP, Minetti CA, Portaliou AG, Economou A, Kalodimos CG
Structural instability tuning as a regulatory mechanism in protein-protein interactions.
Mol. Cell
2011
5
44
734-44
Protein-protein interactions mediate a vast number of cellular processes. Here, we present a regulatory mechanism in protein-protein interactions mediated by finely tuned structural instability and coupled with molecular mimicry. We show that a set of type III secretion (TTS) autoinhibited homodimeric chaperones adopt a molten globule-like state that transiently exposes the substrate binding site as a means to become rapidly poised for binding to their cognate protein substrates. Packing defects at the homodimeric interface stimulate binding, whereas correction of these defects results in less labile chaperones that give rise to nonfunctional biological systems. The protein substrates use structural mimicry to offset the weak spots in the chaperones and to counteract their autoinhibitory conformation. This regulatory mechanism of protein activity is evolutionarily conserved among several TSS systems and presents a lucid example of functional advantage conferred upon a biological system by finely tuned structural instability.
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Coils and zippers
Other
A
L0052
Escherichia coli
MSIVSQTRNKELLDKKIRSEIEAIKKIIAEFDVVKESVNELSEKAKTDPQAAEKLNKLIEGYTYGEERKLYDSALSKIEKLIETLSPARSKSQSTMNQRNRNNRKIV
107
O52124
1
107
100%
UniRef90_O52124
1
107
secondary structure
helix
9
34
secondary structure
helix
44
47
secondary structure
helix
49
55
secondary structure
helix
70
84
pfam
PF11439.5
T3SchapCesA
1
95
B
L0052
Escherichia coli
MSIVSQTRNKELLDKKIRSEIEAIKKIIAEFDVVKESVNELSEKAKTDPQAAEKLNKLIEGYTYGEERKLYDSALSKIEKLIETLSPARSKSQSTMNQRNRNNRKIV
107
O52124
1
107
100%
UniRef90_O52124
1
107
secondary structure
helix
2
4
secondary structure
helix
9
27
secondary structure
helix
31
39
secondary structure
helix
43
47
secondary structure
helix
49
55
secondary structure
helix
72
84
pfam
PF11439.5
T3SchapCesA
1
95
E. coli CesAB was shown to form a loosely packed four-helix bundle stabilized by coiled-coil interactions that are partially disrupted by packing irregularities. Thus native CesAB adopts a molted globule-like structure even in its dimeric state (PMID:22152477).
2m1n
MF2120022
Quorum-sensing antiactivator TraM
1rfy
X-ray
1.60
homodimer
Rhizobium radiobacter
15186414
Chen G, Malenkos JW, Cha MR, Fuqua C, Chen L
Quorum-sensing antiactivator TraM forms a dimer that dissociates to inhibit TraR.
Mol. Microbiol.
2004
6
52
1641-51
The quorum-sensing transcriptional activator TraR of Agrobacterium tumefaciens, which controls the replication and conjugal transfer of the tumour-inducing (Ti) virulence plasmid, is inhibited by the TraM antiactivator. The crystal structure of TraM reveals this protein to form a homodimer in which the monomer primarily consists of two long coiled alpha-helices, and one of the helices from each monomer also bundles to form the dimeric interface. The importance of dimerization is addressed by mutational studies in which disruption of the hydrophobic dimer interface leads to aggregation of TraM. Biochemical studies confirm that TraM exists as a homodimer in solution in equilibrium with the monomeric form, and also establish that the TraM-TraR complex is a heterodimer. Thus, the TraM homodimer undergoes dissociation in forming the antiactivation complex. Combined with the structure of TraR (Zhang et al., 2002, Nature 417: 971-974; Vannini et al., 2002, EMBO J 21: 4393-4401), our structural analysis suggests overlapping interactive surfaces in homodimeric TraM with those in the TraM-TraR complex and a mechanism for TraM inhibition on TraR.
GO:0045892
negative regulation of transcription, DNA-templated
GO:0006351
transcription, DNA-templated
GO:0000746
conjugation
Chain C was generated from chain A using the biomatrix described in the original PDB file. Chain B was removed as chains A and C represent the biologically relevant dimer.
2
1
Coils and zippers
Other
A
Transcriptional repressor TraM
Rhizobium radiobacter
MELEDANVTKKVELRPLIGLTRGLPPTDLETITIDAIRTHRRLVEKADELFQALPETYKTGQACGGPQHIRYIEASIEMHAQMSALNTLISILGFIPKVVVN
102
Q57471
1
102
100%
UniRef90_Q57471
1
102
secondary structure
helix
16
21
secondary structure
helix
26
52
secondary structure
helix
56
59
secondary structure
helix
67
93
pfam
PF09228.7
Prok-TraM
1
99
C
Transcriptional repressor TraM
Rhizobium radiobacter
MELEDANVTKKVELRPLIGLTRGLPPTDLETITIDAIRTHRRLVEKADELFQALPETYKTGQACGGPQHIRYIEASIEMHAQMSALNTLISILGFIPKVVVN
102
Q57471
1
102
100%
UniRef90_Q57471
1
102
secondary structure
helix
16
21
secondary structure
helix
26
52
secondary structure
helix
56
59
secondary structure
helix
67
93
pfam
PF09228.7
Prok-TraM
1
99
TraM dimers were shown to fold/refold in a single step via a two-state mechanism using thermal unfolding experiments monitored by CD (PMID:16997969).
1upg
1us6
MF2120023
Quorum-sensing antiactivator TraM2
2hjd
X-ray
2.10
homodimer
Rhizobium radiobacter
16997969
Chen G, Wang C, Fuqua C, Zhang LH, Chen L
Crystal structure and mechanism of TraM2, a second quorum-sensing antiactivator of Agrobacterium tumefaciens strain A6.
J. Bacteriol.
2006
23
188
8244-51
Quorum sensing is a community behavior that bacteria utilize to coordinate a variety of population density-dependent biological functions. In Agrobacterium tumefaciens, quorum sensing regulates the replication and conjugative transfer of the tumor-inducing (Ti) plasmid from pathogenic strains to nonpathogenic derivatives. Most of the quorum-sensing regulatory proteins are encoded within the Ti plasmid. Among these, TraR is a LuxR-type transcription factor playing a key role as the quorum-sensing signal receptor, and TraM is an antiactivator that antagonizes TraR through the formation of a stable oligomeric complex. Recently, a second TraM homologue called TraM2, not encoded on the Ti plasmid of A. tumefaciens A6, was identified, in addition to a copy on the Ti plasmid. In this report, we have characterized TraM2 and its interaction with TraR and solved its crystal structure to 2.1 A. Like TraM, TraM2 folds into a helical bundle and exists as homodimer. TraM2 forms a stable complex (K(d) = 8.6 nM) with TraR in a 1:1 binding ratio, a weaker affinity than that of TraM for TraR. Structural analysis and biochemical studies suggest that protein stability may account for the difference between TraM2 and TraM in their binding affinities to TraR and provide a structural basis for L54 in promoting structural stability of TraM.
GO:0045892
negative regulation of transcription, DNA-templated
Chains C and D were removed as chains A and B represent the biologically relevant dimer.
2
1
Coils and zippers
Other
A
Quorum-sensing antiactivator
Rhizobium radiobacter
MDLKDSVVSDTFELRPVIGLTRGLSSADIETLTANAIRLHRQLLEKADQLFQVLPDDIKIGTAAGGEQHLEYIEAMIEMHAQMSAVNTLVGLLGFIPKVSVN
102
Q20HX4
1
102
100%
UniRef90_Q20HX4
1
102
secondary structure
helix
16
21
secondary structure
helix
26
52
secondary structure
helix
56
60
secondary structure
helix
67
93
pfam
PF09228.7
Prok-TraM
1
99
B
Quorum-sensing antiactivator
Rhizobium radiobacter
MDLKDSVVSDTFELRPVIGLTRGLSSADIETLTANAIRLHRQLLEKADQLFQVLPDDIKIGTAAGGEQHLEYIEAMIEMHAQMSAVNTLVGLLGFIPKVSVN
102
Q20HX4
1
102
100%
UniRef90_Q20HX4
1
102
secondary structure
helix
16
20
secondary structure
helix
26
52
secondary structure
helix
56
60
secondary structure
helix
67
93
pfam
PF09228.7
Prok-TraM
1
99
TraM dimers were shown to fold/refold in a single step via a two-state mechanism using thermal unfolding experiments monitored by CD (PMID:16997969).
MF5200001
The synaptic acetylcholinesterase tetramer assembled around a polyproline-II helix
1vzj
X-ray
2.35
heteropentamer
Homo sapiens
15526038
Dvir H, Harel M, Bon S, Liu WQ, Vidal M, Garbay C, Sussman JL, Massoulié J, Silman I
The synaptic acetylcholinesterase tetramer assembles around a polyproline II helix.
EMBO J.
2004
22
23
4394-405
Functional localization of acetylcholinesterase (AChE) in vertebrate muscle and brain depends on interaction of the tryptophan amphiphilic tetramerization (WAT) sequence, at the C-terminus of its major splice variant (T), with a proline-rich attachment domain (PRAD), of the anchoring proteins, collagenous (ColQ) and proline-rich membrane anchor. The crystal structure of the WAT/PRAD complex reveals a novel supercoil structure in which four parallel WAT chains form a left-handed superhelix around an antiparallel left-handed PRAD helix resembling polyproline II. The WAT coiled coils possess a WWW motif making repetitive hydrophobic stacking and hydrogen-bond interactions with the PRAD. The WAT chains are related by an approximately 4-fold screw axis around the PRAD. Each WAT makes similar but unique interactions, consistent with an asymmetric pattern of disulfide linkages between the AChE tetramer subunits and ColQ. The P59Q mutation in ColQ, which causes congenital endplate AChE deficiency, and is located within the PRAD, disrupts crucial WAT-WAT and WAT-PRAD interactions. A model is proposed for the synaptic AChE(T) tetramer.
GO:0005515
protein binding
GO:0001507
acetylcholine catabolic process in synaptic cleft
GO:0030054
cell junction
GO:0031594
neuromuscular junction
GO:0005615
extracellular space
GO:0005605
basal lamina
GO:0005886
plasma membrane
GO:0043083
synaptic cleft
Chains E, F, G, H and J were removed as chains A, B, C, D and I represent the biologically relevant oligomer.
5
2
Coils and zippers
Other
A
Acetylcholinesterase
Homo sapiens
DTLDEAERQWKAEFHRWSSYMVHWKNQFDHYSKQDRCSDL
40
P22303
575
614
6.5%
UniRef90_P22303
575
614
secondary structure
helix
580
594
secondary structure
helix
596
602
pfam
PF08674.7
AChE_tetra
578
613
B
Acetylcholinesterase
Homo sapiens
DTLDEAERQWKAEFHRWSSYMVHWKNQFDHYSKQDRCSDL
40
P22303
575
614
6.5%
UniRef90_P22303
575
614
secondary structure
helix
576
586
secondary structure
helix
588
594
secondary structure
helix
596
605
pfam
PF08674.7
AChE_tetra
578
613
C
Acetylcholinesterase
Homo sapiens
DTLDEAERQWKAEFHRWSSYMVHWKNQFDHYSKQDRCSDL
40
P22303
575
614
6.5%
UniRef90_P22303
575
614
secondary structure
helix
576
594
secondary structure
helix
596
606
pfam
PF08674.7
AChE_tetra
578
613
D
Acetylcholinesterase
Homo sapiens
DTLDEAERQWKAEFHRWSSYMVHWKNQFDHYSKQDRCSDL
40
P22303
575
614
6.5%
UniRef90_P22303
575
614
secondary structure
helix
576
594
secondary structure
helix
596
606
pfam
PF08674.7
AChE_tetra
578
613
I
Acetylcholinesterase collagenic tail peptide
Homo sapiens
LLTPPPPPLFPPPFF
15
Q9Y215
53
67
3.3%
UniRef90_Q9Y215
?
?
The subunits in the structure are bound via coiled coil interactions (PMID:15526038). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
MF2140010
Antitoxin phd dimer (Escherichia virus P1)
3hs2
X-ray
2.20
homodimer
Enterobacteria phage P1
20603017
Garcia-Pino A, Balasubramanian S, Wyns L, Gazit E, De Greve H, Magnuson RD, Charlier D, van Nuland NA, Loris R
Allostery and intrinsic disorder mediate transcription regulation by conditional cooperativity.
Cell
2010
1
142
101-11
Regulation of the phd/doc toxin-antitoxin operon involves the toxin Doc as co- or derepressor depending on the ratio between Phd and Doc, a phenomenon known as conditional cooperativity. The mechanism underlying this observed behavior is not understood. Here we show that monomeric Doc engages two Phd dimers on two unrelated binding sites. The binding of Doc to the intrinsically disordered C-terminal domain of Phd structures its N-terminal DNA-binding domain, illustrating allosteric coupling between highly disordered and highly unstable domains. This allosteric effect also couples Doc neutralization to the conditional regulation of transcription. In this way, higher levels of Doc tighten repression up to a point where the accumulation of toxin triggers the production of Phd to counteract its action. Our experiments provide the basis for understanding the mechanism of conditional cooperative regulation of transcription typical of toxin-antitoxin modules. This model may be applicable for the regulation of other biological systems.
GO:0005515
protein binding
GO:0006351
transcription, DNA-templated
GO:0006355
regulation of transcription, DNA-templated
Chains C, D, E, F, G and H were removed as chains A and B represent the biologically relevant dimer.
2
1
Other
Phd antitoxin
A
Antitoxin phd
Enterobacteria phage P1
MQSINFRTARGNLSEVLNNVEAGEEVEITRRGREPAVIVSKATFEAYKKAALDAEFAS
58
Q06253
1
58
79.5%
UniRef90_Q06253
1
58
secondary structure
beta
2
5
secondary structure
helix
6
11
secondary structure
helix
13
21
secondary structure
beta
26
29
secondary structure
beta
36
40
secondary structure
helix
41
55
pfam
PF02604.16
PhdYeFM_antitox
1
70
B
Antitoxin phd
Enterobacteria phage P1
MQSINFRTARGNLSEVLNNVEAGEEVEITRRGREPAVIVSKATFEAYKKAALDAEFAS
58
Q06253
1
58
79.5%
UniRef90_Q06253
1
58
secondary structure
beta
2
5
secondary structure
helix
6
11
secondary structure
helix
13
21
secondary structure
beta
26
30
secondary structure
beta
33
40
secondary structure
helix
41
55
pfam
PF02604.16
PhdYeFM_antitox
1
70
The dimerization of the prevents host death (phd) antitoxin from Escherichia virus P1 has been shown with differential scanning calorimetry to fit well to a two-state model consisting of a dimer unfolding into monomer species (PMID:20603017).
A
The 1-73 region described in DisProt entry DP00288 covers 100% of the sequence present in the structure.
B
The 1-73 region described in DisProt entry DP00288 covers 100% of the sequence present in the structure.
3k33
3kh2
4zlx
4zm0
4zm2
MF2120024
Antitoxin phd dimer (Mycobacterium tuberculosis)
3g5o
X-ray
2.00
homodimer
Mycobacterium tuberculosis
Miallau, L., Chernishof, I., Chiang, J., Arbing, M., Cascio, D., Eisenberg, D.
The crystal structure of the toxin-antitoxin complex RelBE2 (Rv2865-2866) from Mycobacterium tuberculosis
To be published
-
GO:0097351
toxin-antitoxin pair type II binding
GO:0003677
DNA binding
GO:0006351
transcription, DNA-templated
GO:0006355
regulation of transcription, DNA-templated
GO:0045927
positive regulation of growth
Chains B and C were removed as chains A and D represent the biologically relevant dimer. Chains A and D were truncated to exclude the regions in contact with chains B and C.
2
1
Other
Phd antitoxin
A
Antitoxin RelF
Mycobacterium tuberculosis
0
O33347
1
93
100%
UniRef90_O33347
1
93
secondary structure
beta
1
5
secondary structure
helix
6
9
secondary structure
helix
13
21
secondary structure
beta
26
31
secondary structure
beta
34
41
secondary structure
helix
42
55
pfam
PF02604.16
PhdYeFM_antitox
1
74
D
Antitoxin RelF
Mycobacterium tuberculosis
0
O33347
1
93
100%
UniRef90_O33347
1
93
secondary structure
beta
1
5
secondary structure
helix
6
9
secondary structure
helix
13
21
secondary structure
beta
26
31
secondary structure
beta
34
41
secondary structure
helix
42
55
pfam
PF02604.16
PhdYeFM_antitox
1
74
The dimerization of the prevents host death (phd) antitoxin from Escherichia virus P1 has been shown with differential scanning calorimetry to fit well to a two-state model consisting of a dimer unfolding into monomer species (PMID:20603017).
A
A homologue sharing the same Pfam domain (PF02604.16) has been experimentally characterized as disordered in DisProt entry DP00288.
D
A homologue sharing the same Pfam domain (PF02604.16) has been experimentally characterized as disordered in DisProt entry DP00288.
MF2120025
Docking domain A of the erythronolide synthase
1pzq
NMR
homodimer
Saccharopolyspora erythraea
12954331
Broadhurst RW, Nietlispach D, Wheatcroft MP, Leadlay PF, Weissman KJ
The structure of docking domains in modular polyketide synthases.
Chem. Biol.
2003
8
10
723-31
Polyketides from actinomycete bacteria provide the basis for many valuable medicines, so engineering genes for their biosynthesis to produce variant molecules holds promise for drug discovery. The modular polyketide synthases are particularly amenable to this approach, because each cycle of chain extension is catalyzed by a different module of enzymes, and the modules are arranged within giant multienzyme subunits in the order in which they act. Protein-protein interactions between terminal docking domains of successive multienzymes promote their correct positioning within the assembly line, but because the overall complex is not stable in vitro, the key interactions have not been identified. We present here the NMR solution structure of a 120 residue polypeptide representing a typical pair of such domains, fused at their respective C and N termini: it adopts a stable dimeric structure which reveals the detailed role of these (predominantly helical) domains in docking and dimerization by modular polyketide synthases.
GO:0031177
phosphopantetheine binding
GO:0016491
oxidoreductase activity
GO:0048037
cofactor binding
GO:0047879
erythronolide synthase activity
GO:0055114
oxidation-reduction process
GO:0033068
macrolide biosynthetic process
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Coils and zippers
Coiled coil (dimeric, forming a 4-helix bundle)
A
Erythronolide synthase, modules 3 and 4
Saccharopolyspora erythraea
GSAASPAVDIGDRLDELEKALEALSAEDGHDDVGQRLESLLRRWNSRRADAPSTSAISED
60
Q03132
3488
3547
1.7%
UniRef90_Q03132
3490
3547
secondary structure
helix
3498
3511
secondary structure
helix
3518
3536
pfam
PF09277.8
Erythro-docking
3490
3547
B
Erythronolide synthase, modules 3 and 4
Saccharopolyspora erythraea
GSAASPAVDIGDRLDELEKALEALSAEDGHDDVGQRLESLLRRWNSRRADAPSTSAISED
60
Q03132
3488
3547
1.7%
UniRef90_Q03132
3490
3547
secondary structure
helix
3498
3511
secondary structure
helix
3518
3536
pfam
PF09277.8
Erythro-docking
3490
3547
The subunits in the structure are bound via coiled coil interactions (PMID:12954331). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
MF2100012
Human glutathione S-transferase A1
1k3y
X-ray
1.30
homodimer
Homo sapiens
12211029
Le Trong I, Stenkamp RE, Ibarra C, Atkins WM, Adman ET
1.3-A resolution structure of human glutathione S-transferase with S-hexyl glutathione bound reveals possible extended ligandin binding site.
Proteins
2002
4
48
618-27
Cytosolic glutathione S-transferases (GSTs) play a critical role in xenobiotic binding and metabolism, as well as in modulation of oxidative stress. Here, the high-resolution X-ray crystal structures of homodimeric human GSTA1-1 in the apo form and in complex with S-hexyl glutathione (two data sets) are reported at 1.8, 1.5, and 1.3A respectively. At this level of resolution, distinct conformations of the alkyl chain of S-hexyl glutathione are observed, reflecting the nonspecific nature of the hydrophobic substrate binding site (H-site). Also, an extensive network of ordered water, including 75 discrete solvent molecules, traverses the open subunit-subunit interface and connects the glutathione binding sites in each subunit. In the highest-resolution structure, three glycerol moieties lie within this network and directly connect the amino termini of the glutathione molecules. A search for ligand binding sites with the docking program Molecular Operating Environment identified the ordered water network binding site, lined mainly with hydrophobic residues, suggesting an extended ligand binding surface for nonsubstrate ligands, the so-called ligandin site. Finally, detailed comparison of the structures reported here with previously published X-ray structures reveal a possible reaction coordinate for ligand-dependent conformational changes in the active site and the C-terminus.
GO:0004364
glutathione transferase activity
GO:0004602
glutathione peroxidase activity
GO:0006749
glutathione metabolic process
GO:0098869
cellular oxidant detoxification
GO:0043651
linoleic acid metabolic process
GO:1901687
glutathione derivative biosynthetic process
GO:0030855
epithelial cell differentiation
GO:0070062
extracellular exosome
GO:0005829
cytosol
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Homooligomeric enzymes
Homodimeric enzymes
A
Glutathione S-transferase A1
Homo sapiens
AEKPKLHYFNARGRMESTRWLLAAAGVEFEEKFIKSAEDLDKLRNDGYLMFQQVPMVEIDGMKLVQTRAILNYIASKYNLYGKDIKERALIDMYIEGIADLGEMILLLPVCPPEEKDAKLALIKEKIKNRYFPAFEKVLKSHGQDYLVGNKLSRADIHLVELLYYVEELDSSLISSFPLLKALKTRISNLPTVKKFLQPGSPRKPPMDEKSLEEARKIFRF
221
P08263
2
222
99.5%
UniRef90_P08263
2
222
secondary structure
beta
6
10
secondary structure
helix
17
26
secondary structure
beta
31
35
secondary structure
helix
38
46
secondary structure
beta
57
60
secondary structure
beta
63
66
secondary structure
helix
68
78
secondary structure
helix
86
111
secondary structure
helix
114
143
secondary structure
helix
155
170
secondary structure
helix
179
190
secondary structure
helix
192
198
secondary structure
helix
210
220
pfam
PF02798.17
GST_N
5
77
pfam
PF00043.22
GST_C
99
192
B
Glutathione S-transferase A1
Homo sapiens
AEKPKLHYFNARGRMESTRWLLAAAGVEFEEKFIKSAEDLDKLRNDGYLMFQQVPMVEIDGMKLVQTRAILNYIASKYNLYGKDIKERALIDMYIEGIADLGEMILLLPVCPPEEKDAKLALIKEKIKNRYFPAFEKVLKSHGQDYLVGNKLSRADIHLVELLYYVEELDSSLISSFPLLKALKTRISNLPTVKKFLQPGSPRKPPMDEKSLEEARKIFRF
221
P08263
2
222
99.5%
UniRef90_P08263
2
222
secondary structure
beta
6
9
secondary structure
helix
17
25
secondary structure
beta
31
34
secondary structure
helix
38
46
secondary structure
beta
57
60
secondary structure
beta
63
66
secondary structure
helix
68
78
secondary structure
helix
86
111
secondary structure
helix
114
143
secondary structure
helix
155
170
secondary structure
helix
179
190
secondary structure
helix
192
198
secondary structure
helix
210
220
pfam
PF02798.17
GST_N
5
77
pfam
PF00043.22
GST_C
99
192
The urea-induced unfolding/refolding of human glutathione S-transferase A1 dimer has been shown to be a two-state process (PMID:9548764) with the association of disordered monomers forming a structured dimer. While there may be some structuring of the monomers before dimerization, this partial structure does not fully stabilize the protein (PMID:10600132).
1gsd
1gse
1gsf
1guh
1k3l
1k3o
1lbk
1pkw
1pkz
1pl1
1pl2
1usb
1xwg
1ydk
2r3x
2r6k
3i69
3i6a
3ik9
3ktl
3l0h
3q74
3u6v
3zfb
3zfl
4hj2
5jcu
5lcz
5ld0
MF2130001
Archaeal histone hMfB
1bfm
NMR
homodimer
Methanothermus fervidus
8568866
Starich MR, Sandman K, Reeve JN, Summers MF
NMR structure of HMfB from the hyperthermophile, Methanothermus fervidus, confirms that this archaeal protein is a histone.
J. Mol. Biol.
1996
1
255
187-203
The three-dimensional structure of the recombinant histone rHMfB from Methanothermus fervidus, an archaeon that grows optimally at 83 degrees C, has been determined by nuclear magnetic resonance methods. This is only the third structure of a protein from a hyperthermophilic organism (optimal growth at temperatures above 80 degrees C). Signal assignments were made using a combination of homonuclear-correlated, 15N-double resonance and 15N, 13C triple resonance NMR experiments. Long range dipolar interactions for the symmetric homodimer were identified from two-dimensional 13C-double half-filtered and three-dimensional 13C-filtered NMR data obtained for a heterolabeled-dimer. A family of 33 structures was calculated using DSPACE with a total of 609 NOE-derived interproton distance restraints, including 22 intraresidue, 192 sequential, 300 medium-range (two to five residues), 86 long-range intramolecular (more than five residues) and 112 intermolecular distance restraints. The monomer subunits consist of three alpha-helices, extending from residues Pro4 to Ala15 (helix I), Ser21 to Ala50 (helix II) and Lys56 to Lys68 (helix III), as well as two short segments of beta-strand comprised of residues Arg19 to Ser21 and Thr54 to Ile55. Helices I, II and III contain N-terminal capping boxes, and helices I and II contain C-terminal caps. The structure of the (rHMfB)2 dimer appears very similar to the dimer subunits within the histone core octamer of the chicken nucleosome. The presence of a canonical "histone fold" motif in rHMfB is consistent with the HMf family of archaeal histones and the eukaryal nucleosome core histones having evolved from a common ancestor. The (rHMfB)2 dimer contains several structural features that may impart thermal stability (or non-lability), including two novel hydrophobic "proline Ncaps", four interhelical hydrogen bonds and short N- and C-terminal disordered tails.
GO:0046982
protein heterodimerization activity
GO:0003677
DNA binding
GO:0005737
cytoplasm
GO:0005694
chromosome
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Histone-like interactions
Histone-like complexes
A
DNA-binding protein HMf-2
Methanothermus fervidus
MELPIAPIGRIIKDAGAERVSDDARITLAKILEEMGRDIASEAIKLARHAGRKTIKAEDIELAVRRFKK
69
P19267
1
69
100%
UniRef90_P19267
1
69
secondary structure
helix
5
15
secondary structure
beta
19
20
secondary structure
helix
22
50
secondary structure
beta
55
55
secondary structure
helix
57
67
pfam
PF00808.20
CBFD_NFYB_HMF
1
64
B
DNA-binding protein HMf-2
Methanothermus fervidus
MELPIAPIGRIIKDAGAERVSDDARITLAKILEEMGRDIASEAIKLARHAGRKTIKAEDIELAVRRFKK
69
P19267
1
69
100%
UniRef90_P19267
1
69
secondary structure
helix
5
15
secondary structure
beta
20
20
secondary structure
helix
22
50
secondary structure
beta
54
55
secondary structure
helix
57
67
pfam
PF00808.20
CBFD_NFYB_HMF
1
64
The GdmCl-induced unfolding and refolding transitions of the dimer (monitored by stopped-flow far UV CD) provide support for a two-state equilibrium reaction with no populated intermediates. The data sets were well described by the global fits to a two-state model (PMID:15313621).
1a7w
1b6w
MF2100013
S100B
1uwo
NMR
homodimer
Homo sapiens
9519411
Smith SP, Shaw GS
A novel calcium-sensitive switch revealed by the structure of human S100B in the calcium-bound form.
Structure
1998
2
6
211-22
CONCLUSIONS: The calcium-induced reorientation of calcium-binding site II results in the increased exposure of several hydrophobic residues in helix IV and the linker region. While following the general mechanism of calcium modulatory proteins, whereby a hydrophobic target site is exposed, the 'calcium switch' observed in S100B appears to be unique from that of other EF-hand proteins and may provide insights into target specificity among calcium modulatory proteins. RESULTS: The solution structure of calcium-saturated human S100B (Ca(2+)-S100B) has been determined by heteronuclear NMR spectroscopy. Ca(2+)-S100B forms a well defined globular structure comprising four EF-hand calcium-binding sites and an extensive hydrophobic dimer interface. A comparison of Ca(2+)-S100B with apo S100B and Ca(2+)-calbindin D9k indicates that while calcium-binding to S100B results in little change in the site I EF-hand, it induces a backbone reorientation of the N terminus of the site II EF-hand. This reorientation leads to a dramatic change in the position of helix III relative to the other helices. BACKGROUND: S100B is a homodimeric member of the EF-hand calcium-binding protein superfamily. The protein has been implicated in cellular processes such as cell differentiation and growth, plays a role in cytoskeletal structure and function, and may have a role in neuropathological diseases, such as Alzheimers. The effects of S100B are mediated via its interaction with target proteins. While several studies have suggested that this interaction is propagated through a calcium-induced conformational change, leading to the exposure of a hydrophobic region of S100B, the molecular details behind this structural alteration remain unclear.
GO:0050786
RAGE receptor binding
GO:0042803
protein homodimerization activity
GO:0008270
zinc ion binding
GO:0048156
tau protein binding
GO:0048306
calcium-dependent protein binding
GO:0044548
S100 protein binding
GO:0005509
calcium ion binding
GO:0045087
innate immune response
GO:0008284
positive regulation of cell proliferation
GO:0008283
cell proliferation
GO:0043123
positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0071456
cellular response to hypoxia
GO:0060291
long-term synaptic potentiation
GO:2001015
negative regulation of skeletal muscle cell differentiation
GO:0007409
axonogenesis
GO:0048708
astrocyte differentiation
GO:0051384
response to glucocorticoid
GO:0008360
regulation of cell shape
GO:0043065
positive regulation of apoptotic process
GO:0051597
response to methylmercury
GO:0048168
regulation of neuronal synaptic plasticity
GO:0007613
memory
GO:0005634
nucleus
GO:0043025
neuronal cell body
GO:0001726
ruffle
GO:0005615
extracellular space
GO:0048471
perinuclear region of cytoplasm
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Other
Other
A
Protein S100-B
Homo sapiens
SELEKAMVALIDVFHQYSGREGDKHKLKKSELKELINNELSHFLEEIKEQEVVDKVMETLDNDGDGECDFQEFMAFVAMVTTACHEFFEHE
91
P04271
2
92
98.9%
UniRef90_P04271
2
92
secondary structure
helix
3
21
secondary structure
beta
29
29
secondary structure
helix
31
40
secondary structure
helix
53
61
secondary structure
beta
68
68
secondary structure
helix
71
87
pfam
PF01023.16
S_100
4
46
pfam
PF00036.29
EF-hand_1
53
81
B
Protein S100-B
Homo sapiens
SELEKAMVALIDVFHQYSGREGDKHKLKKSELKELINNELSHFLEEIKEQEVVDKVMETLDNDGDGECDFQEFMAFVAMVTTACHEFFEHE
91
P04271
2
92
98.9%
UniRef90_P04271
2
92
secondary structure
helix
3
18
secondary structure
helix
30
40
secondary structure
helix
53
60
secondary structure
beta
62
62
secondary structure
beta
69
69
secondary structure
helix
71
89
pfam
PF01023.16
S_100
4
46
pfam
PF00036.29
EF-hand_1
53
81
GuHCl-induced denaturation of the S100B protein dimer showed that it follows a two-state unfolding/refolding process (PMID:11888280).
3czt
3d0y
3d10
2h61
3hcm
2m49
1mq1
2pru
4xyn
5csf
5csi
5csj
5csn
5d7f
MF2110016
Dynein light chain TcTex-1
1ygt
X-ray
1.70
homodimer
Drosophila melanogaster
15701632
Williams JC, Xie H, Hendrickson WA
Crystal structure of dynein light chain TcTex-1.
J. Biol. Chem.
2005
23
280
21981-6
TcTex-1, one of three dynein light chains of the dynein motor complex, has been implicated in targeting and binding cargoes to cytoplasmic dynein for retrograde or apical transport. Interactions between TcTex-1 and a diverse set of proteins such as the dynein intermediate chain, Fyn, DOC2, FIP1, the poliovirus receptor, CD155, and the rhodopsin cytoplasmic tail have been reported; yet, despite the broad range of targets, a consensus binding sequence remains uncertain. Consequently, we have solved the crystal structure of the full-length Drosophila homolog of TcTex-1 to 1.7 A resolution using MAD phasing to gain insight into its function and target specificity. The structure is homodimeric with a domain swapping of beta-strand 2 and has a fold similar to the dynein light chain, LC8. Based on structural alignment, the TcTex-1 and LC8 sequences show no identity, although the root mean square deviation between secondary structural elements is less than 1.6 A. Moreover, the N terminus, which is equivalent to beta-strand 1 in LC8, is splayed out and binds to a crystallographic dimer as an anti-parallel beta-strand at the same position as the neuronal nitric-oxide synthase peptide in the LC8 complex. Similarity to LC8 and comparison to the LC8-neuronal nitricoxide synthase complex suggest that TcTex-1 binds its targets in a similar manner as LC8 and provides insight to the lack of strict sequence identity among the targets for TcTex-1.
GO:0045505
dynein intermediate chain binding
GO:0042623
ATPase activity, coupled
GO:0051959
dynein light intermediate chain binding
GO:0003774
motor activity
GO:0042803
protein homodimerization activity
GO:0008090
retrograde axonal transport
GO:0007286
spermatid development
GO:0007067
mitotic nuclear division
GO:0008340
determination of adult lifespan
GO:1904115
axon cytoplasm
GO:0005874
microtubule
GO:0005868
cytoplasmic dynein complex
Chain B was generated from chain A using the biomatrix described in the original PDB file.
2
1
Other
Other
A
Dynein light chain Tctex-type
Drosophila melanogaster
MDDSREESQFIVDDVSKTIKEAIETTIGGNAYQHDKVNNWTGQVVENCLTVLTKEQKPYKYIVTAMIMQKNGAGLHTASSCYWNNDTDGSCTVRWENKTMYCIVSVFGLAV
111
Q94524
1
111
100%
UniRef90_Q94524
1
111
secondary structure
helix
14
27
secondary structure
helix
34
53
secondary structure
beta
59
69
secondary structure
beta
75
82
secondary structure
beta
89
96
secondary structure
beta
100
110
pfam
PF03645.10
Tctex-1
14
110
B
Dynein light chain Tctex-type
Drosophila melanogaster
MDDSREESQFIVDDVSKTIKEAIETTIGGNAYQHDKVNNWTGQVVENCLTVLTKEQKPYKYIVTAMIMQKNGAGLHTASSCYWNNDTDGSCTVRWENKTMYCIVSVFGLAV
111
Q94524
1
111
100%
UniRef90_Q94524
1
111
secondary structure
helix
14
27
secondary structure
helix
34
53
secondary structure
beta
59
69
secondary structure
beta
75
82
secondary structure
beta
89
96
secondary structure
beta
100
110
pfam
PF03645.10
Tctex-1
14
110
The equilibrium unfolding transition of the dynein light chain TcTex-1 dimer was monitored by intrinsic fluorescence intensity, fluorescence anisotropy, and circular dichroism and was modeled as a two-state mechanism where a folded dimer dissociates to two unfolded monomers without populating thermodynamically stable monomeric or dimeric intermediates (PMID:16734416).
3fm7
2pg1
MF2120026
Dihydrofolate reductase
1cz3
X-ray
2.10
homodimer
Thermotoga maritima
10731419
Dams T, Auerbach G, Bader G, Jacob U, Ploom T, Huber R, Jaenicke R
The crystal structure of dihydrofolate reductase from Thermotoga maritima: molecular features of thermostability.
J. Mol. Biol.
2000
3
297
659-72
Two high-resolution structures have been obtained for dihydrofolate reductase from the hyperthermophilic bacterium Thermotoga maritima in its unliganded state, and in its ternary complex with the cofactor NADPH and the inhibitor, methotrexate. While the overall fold of the hyperthermophilic enzyme is closely similar to monomeric mesophilic dihydrofolate reductase molecules, its quaternary structure is exceptional, in that T. maritima dihydrofolate reductase forms a highly stable homodimer. Here, the molecular reasons for the high intrinsic stability of the enzyme are elaborated and put in context with the available data on the physical parameters governing the folding reaction. The molecule is extremely rigid, even with respect to structural changes during substrate binding and turnover. Subunit cooperativity can be excluded from structural and biochemical data. Major contributions to the high intrinsic stability of the enzyme result from the formation of the dimer. Within the monomer, only subtle stabilizing interactions are detectable, without clear evidence for any of the typical increments of thermal stabilization commonly reported for hyperthermophilic proteins. The docking of the subunits is optimized with respect to high packing density in the dimer interface, additional salt-bridges and beta-sheets. The enzyme does not show significant structural changes upon binding its coenzyme, NADPH, and the inhibitor, methotrexate. The active-site loop, which is known to play an important role in catalysis in mesophilic dihydrofolate reductase molecules, is rearranged, participating in the association of the subunits; it no longer participates in catalysis.
GO:0050661
NADP binding
GO:0004146
dihydrofolate reductase activity
GO:0006730
one-carbon metabolic process
GO:0006545
glycine biosynthetic process
GO:0055114
oxidation-reduction process
GO:0009165
nucleotide biosynthetic process
GO:0046654
tetrahydrofolate biosynthetic process
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Homooligomeric enzymes
Homodimeric enzymes
A
Dihydrofolate reductase
Thermotoga maritima
AKVIFVLAMDVSGKIASSVESWSSFEDRKNFRKITTEIGNVVMGRITFEEIGRPLPERLNVVLTRRPKTSNNPSLVFFNGSPADVVKFLEGKGYERVAVIGGKTVFTEFLREKLVDELFVTVEPYVFGKGIPFFDEFEGYFPLKLLEMRRLNERGTLFLKYSVEKSHR
168
Q60034
2
165
97%
UniRef90_Q60034
2
165
secondary structure
beta
3
10
secondary structure
beta
15
17
secondary structure
helix
26
39
secondary structure
beta
41
45
secondary structure
helix
46
52
secondary structure
beta
60
64
secondary structure
beta
76
79
secondary structure
helix
83
92
secondary structure
beta
97
102
secondary structure
helix
104
112
secondary structure
beta
118
123
secondary structure
beta
126
128
secondary structure
beta
132
133
secondary structure
beta
141
151
secondary structure
beta
158
164
pfam
PF00186.16
DHFR_1
3
150
B
Dihydrofolate reductase
Thermotoga maritima
AKVIFVLAMDVSGKIASSVESWSSFEDRKNFRKITTEIGNVVMGRITFEEIGRPLPERLNVVLTRRPKTSNNPSLVFFNGSPADVVKFLEGKGYERVAVIGGKTVFTEFLREKLVDELFVTVEPYVFGKGIPFFDEFEGYFPLKLLEMRRLNERGTLFLKYSVEKSHR
168
Q60034
2
165
97%
UniRef90_Q60034
2
165
secondary structure
beta
3
10
secondary structure
beta
15
17
secondary structure
helix
26
39
secondary structure
beta
41
45
secondary structure
helix
46
52
secondary structure
beta
60
64
secondary structure
beta
76
79
secondary structure
helix
83
91
secondary structure
beta
97
102
secondary structure
helix
104
112
secondary structure
beta
118
123
secondary structure
beta
126
128
secondary structure
beta
132
133
secondary structure
beta
141
151
secondary structure
beta
158
164
pfam
PF00186.16
DHFR_1
3
150
The enzyme DHFR from the hyperthermophilic bacterium Thermotoga maritima represents an extremely stable dimer; no isolated structured monomers could be detected in equilibrium or during unfolding. The equilibrium unfolding strictly follows the two-state model for the dimer (PMID:10413491).
1d1g
MF4120007
Type II dihydrofolate reductase
2rh2
X-ray
0.96
homotetramer
Escherichia coli
18052202
Krahn JM, Jackson MR, DeRose EF, Howell EE, London RE
Crystal structure of a type II dihydrofolate reductase catalytic ternary complex.
Biochemistry
2007
51
46
14878-88
Type II dihydrofolate reductase (DHFR) is a plasmid-encoded enzyme that confers resistance to bacterial DHFR-targeted antifolate drugs. It forms a symmetric homotetramer with a central pore which functions as the active site. Its unusual structure, which results in a promiscuous binding surface that accommodates either the dihydrofolate (DHF) substrate or the NADPH cofactor, has constituted a significant limitation to efforts to understand its substrate specificity and reaction mechanism. We describe here the first structure of a ternary R67 DHFR.DHF.NADP+ catalytic complex, resolved to 1.26 A. This structure provides the first clear picture of how this enzyme, which lacks the active site carboxyl residue that is ubiquitous in Type I DHFRs, is able to function. In the catalytic complex, the polar backbone atoms of two symmetry-related I68 residues provide recognition motifs that interact with the carboxamide on the nicotinamide ring, and the N3-O4 amide function on the pteridine ring. This set of interactions orients the aromatic rings of substrate and cofactor in a relative endo geometry in which the reactive centers are held in close proximity. Additionally, a central, hydrogen-bonded network consisting of two pairs of Y69-Q67-Q67'-Y69' residues provides an unusually tight interface, which appears to serve as a "molecular clamp" holding the substrates in place in an orientation conducive to hydride transfer. In addition to providing the first clear insight regarding how this extremely unusual enzyme is able to function, the structure of the ternary complex provides general insights into how a mutationally challenged enzyme, i.e., an enzyme whose evolution is restricted to four-residues-at-a-time active site mutations, overcomes this fundamental limitation.
GO:0004146
dihydrofolate reductase activity
GO:0006730
one-carbon metabolic process
GO:0042493
response to drug
GO:0031427
response to methotrexate
GO:0055114
oxidation-reduction process
GO:0046654
tetrahydrofolate biosynthetic process
GO:0046677
response to antibiotic
Chains B, C and D were generated from chain A using the biomatrices described in the original PDB file.
4
1
Homooligomeric enzymes
Homotetrameric enzymes
A
Dihydrofolate reductase type 2
Escherichia coli
VFPSNATFGMGDRVRKKSGAAWQGQIVGWYCTNLTPEGYAVESEAHPGSVQIYPVAALERIN
62
P00383
17
78
79.5%
UniRef90_P00383
17
78
secondary structure
beta
28
31
secondary structure
beta
38
45
secondary structure
beta
53
58
secondary structure
beta
65
69
secondary structure
helix
70
72
secondary structure
beta
73
75
pfam
PF06442.8
DHFR_2
1
78
B
Dihydrofolate reductase type 2
Escherichia coli
VFPSNATFGMGDRVRKKSGAAWQGQIVGWYCTNLTPEGYAVESEAHPGSVQIYPVAALERIN
62
P00383
17
78
79.5%
UniRef90_P00383
17
78
secondary structure
beta
28
31
secondary structure
beta
38
45
secondary structure
beta
53
58
secondary structure
beta
65
69
secondary structure
helix
70
72
secondary structure
beta
73
75
pfam
PF06442.8
DHFR_2
1
78
C
Dihydrofolate reductase type 2
Escherichia coli
VFPSNATFGMGDRVRKKSGAAWQGQIVGWYCTNLTPEGYAVESEAHPGSVQIYPVAALERIN
62
P00383
17
78
79.5%
UniRef90_P00383
17
78
secondary structure
beta
28
31
secondary structure
beta
38
45
secondary structure
beta
53
58
secondary structure
beta
65
69
secondary structure
helix
70
72
secondary structure
beta
73
75
pfam
PF06442.8
DHFR_2
1
78
D
Dihydrofolate reductase type 2
Escherichia coli
VFPSNATFGMGDRVRKKSGAAWQGQIVGWYCTNLTPEGYAVESEAHPGSVQIYPVAALERIN
62
P00383
17
78
79.5%
UniRef90_P00383
17
78
secondary structure
beta
28
31
secondary structure
beta
38
45
secondary structure
beta
53
58
secondary structure
beta
65
69
secondary structure
helix
70
72
secondary structure
beta
73
75
pfam
PF06442.8
DHFR_2
1
78
Using absorbance, fluorescence, and circular dichroism the unfolding of type II DHFR is protein concentration dependent and can be described by a two-state model involving native dimer and unfolded monomer (PMID:1932013).
2gqv
2p4t
2rk1
2rk2
3sfm
1vie
1vif
MF2110017
Class pi glutathione S-transferase (Sus scrofa)
2gsr
X-ray
2.11
homodimer
Sus scrofa
7932743
Dirr H, Reinemer P, Huber R
Refined crystal structure of porcine class Pi glutathione S-transferase (pGST P1-1) at 2.1 A resolution.
J. Mol. Biol.
1994
1
243
72-92
The crystal structure of class Pi glutathione S-transferase from porcine lung (pGST P1-1) in complex with glutathione sulphonate has been refined at 2.11 A resolution, to a crystallographic R-factor of 16.5% for 21, 165 unique reflections. The refined structure includes 3314 protein atoms, 46 inhibitor (glutathione sulphonate) atoms and 254 water molecules. The model shows good stereochemistry, with root-mean-square deviations from ideal bond lengths and bond angles of 0.011 A and 2.8 degrees, respectively. The estimated root-mean-square co-ordinate error is 0.2 A. The protein is a dimer assembled from identical subunits of 207 amino acid residues. The tertiary structure of the pGST P1 subunit is organized as two domains, the N-terminal domain (domain I, residues 1 to 74) and the larger C-terminal domain (domain II, residues 81 to 207). Glutathione sulphonate, a competitive inhibitor, binds to the G-site region (i.e. the glutathione-binding region) of the active site located on each subunit. Each G-site is, however, structurally dependent of the neighbouring subunit as structural elements forming a fully functional G-site are provided by both subunits, with domain I as the major supporting framework. A number of direct and water-mediated polar interactions are involved in sequestering the glutathione analogue at the G-site. The extended conformation assumed by the enzyme-bound inhibitor as well as the strategic interactions between inhibitor and protein, closely resemble those observed for the physiological substrate, reduced glutathione bound at the active site of class Mu glutathione S-transferase 3-3. Hydrogen bonding between the sulphonyl moiety of the inhibitor and the hydroxyl group of an evolutionary conserved tyrosine residue, Tyr7, provides the first direct structural evidence for a catalytic protein group in glutathione S-transferases that is involved in the activation of the substrate glutathione. The catalytic role for Tyr7 has subsequently been confirmed by mutagenesis and kinetic studies. Comparison of the known crystal structures for class Pi, class Mu and class Alpha isoenzymes, indicates that the cytosolic glutathione S-transferases share a common fold and that the structural features for catalysis are similar.
GO:0004364
glutathione transferase activity
GO:0008152
metabolic process
GO:0005739
mitochondrion
GO:0005634
nucleus
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Homooligomeric enzymes
Homodimeric enzymes
A
Glutathione S-transferase P
Sus scrofa
PPYTITYFPVRGRCEAMRMLLADQDQSWKEEVVTMETWPPLKPSCLFRQLPKFQDGDLTLYQSNAILRHLGRSFGLYGKDQKEAALVDMVNDGVEDLRCKYATLIYTNYEAGKEKYVKELPEHLKPFETLLSQNQGGQAFVVGSQISFADYNLLDLLRIHQVLNPSCLDAFPLLSAYVARLSARPKIKAFLASPEHVNRPINGNGKQ
207
P80031
1
206
99.5%
UniRef90_P80031
1
206
secondary structure
beta
3
7
secondary structure
helix
15
23
secondary structure
beta
29
32
secondary structure
helix
38
44
secondary structure
beta
52
55
secondary structure
beta
58
61
secondary structure
helix
63
74
secondary structure
helix
81
107
secondary structure
helix
109
132
secondary structure
helix
135
137
secondary structure
helix
148
163
secondary structure
helix
167
170
secondary structure
helix
172
182
secondary structure
helix
185
192
secondary structure
helix
194
197
pfam
PF02798.17
GST_N
3
72
pfam
PF14497.3
GST_C_3
95
194
B
Glutathione S-transferase P
Sus scrofa
PPYTITYFPVRGRCEAMRMLLADQDQSWKEEVVTMETWPPLKPSCLFRQLPKFQDGDLTLYQSNAILRHLGRSFGLYGKDQKEAALVDMVNDGVEDLRCKYATLIYTNYEAGKEKYVKELPEHLKPFETLLSQNQGGQAFVVGSQISFADYNLLDLLRIHQVLNPSCLDAFPLLSAYVARLSARPKIKAFLASPEHVNRPINGNGKQ
207
P80031
1
206
99.5%
UniRef90_P80031
1
206
secondary structure
beta
3
7
secondary structure
helix
12
23
secondary structure
beta
29
32
secondary structure
helix
38
44
secondary structure
beta
52
55
secondary structure
beta
58
61
secondary structure
helix
63
74
secondary structure
helix
81
133
secondary structure
helix
135
137
secondary structure
helix
148
163
secondary structure
helix
172
182
secondary structure
helix
185
192
secondary structure
helix
194
197
pfam
PF02798.17
GST_N
3
72
pfam
PF14497.3
GST_C_3
95
194
Guanidine hydrochloride and urea induced denaturation of the dimer is well described by a two-state model involving significant populations of only the folded dimer and unfolded monomer. Neither a folded, active monomeric form nor stable unfolding intermediates were detected (PMID:1930226).
MF2110018
Glutathione S-transferase (Schistosoma japonicum)
4wr4
X-ray
1.60
homodimer
Schistosoma japonicum
25985257
Ohtake K, Yamaguchi A, Mukai T, Kashimura H, Hirano N, Haruki M, Kohashi S, Yamagishi K, Murayama K, Tomabechi Y, Itagaki T, Akasaka R, Kawazoe M, Takemoto C, Shirouzu M, Yokoyama S, Sakamoto K
Protein stabilization utilizing a redefined codon.
Sci Rep
2015
5
9762
Recent advances have fundamentally changed the ways in which synthetic amino acids are incorporated into proteins, enabling their efficient and multiple-site incorporation, in addition to the 20 canonical amino acids. This development provides opportunities for fresh approaches toward addressing fundamental problems in bioengineering. In the present study, we showed that the structural stability of proteins can be enhanced by integrating bulky halogenated amino acids at multiple selected sites. Glutathione S-transferase was thus stabilized significantly (by 5.2 and 5.6 kcal/mol) with 3-chloro- and 3-bromo-l-tyrosines, respectively, incorporated at seven selected sites. X-ray crystallographic analyses revealed that the bulky halogen moieties filled internal spaces within the molecules, and formed non-canonical stabilizing interactions with the neighboring residues. This new mechanism for protein stabilization is quite simple and applicable to a wide range of proteins, as demonstrated by the rapid stabilization of the industrially relevant azoreductase.
GO:0004364
glutathione transferase activity
Chain B was generated from chain A using the biomatrix described in the original PDB file.
2
1
Homooligomeric enzymes
Homodimeric enzymes
A
Glutathione S-transferase class-mu 26 kDa isozyme
Schistosoma japonicum
MASMTGGQQMGRDPGANSGVTKNSYSPILGYWKIKGLVQPTRLLLEYLEEKYEEHLYERDEGDKWRNKKFELGLEFPNLPYYIDGDVKLTQSMAIIRYIADKHNMLGGCPKERAEISMLEGAVLDIRYGVSRIAYSKDFETLKVDFLSKLPEMLKMFEDRLCHKTYLNGDHVTHPDFMLYDALDVVLYMDPMCLDAFPKLVCFKKRIEAIPQIDKYLKSSKYIAWPLQGWQATFGGGDHPPKSD
244
P08515
2
217
99.1%
UniRef90_P08515
2
217
secondary structure
beta
5
9
secondary structure
helix
13
24
secondary structure
beta
31
36
secondary structure
helix
41
45
secondary structure
beta
61
63
secondary structure
beta
68
70
secondary structure
helix
72
73
secondary structure
helix
75
83
secondary structure
helix
91
112
secondary structure
helix
120
141
secondary structure
beta
148
148
secondary structure
beta
151
151
secondary structure
helix
156
163
secondary structure
helix
165
172
secondary structure
helix
181
191
secondary structure
helix
194
200
pfam
PF02798.17
GST_N
3
77
pfam
PF14497.3
GST_C_3
100
196
B
Glutathione S-transferase class-mu 26 kDa isozyme
Schistosoma japonicum
MASMTGGQQMGRDPGANSGVTKNSYSPILGYWKIKGLVQPTRLLLEYLEEKYEEHLYERDEGDKWRNKKFELGLEFPNLPYYIDGDVKLTQSMAIIRYIADKHNMLGGCPKERAEISMLEGAVLDIRYGVSRIAYSKDFETLKVDFLSKLPEMLKMFEDRLCHKTYLNGDHVTHPDFMLYDALDVVLYMDPMCLDAFPKLVCFKKRIEAIPQIDKYLKSSKYIAWPLQGWQATFGGGDHPPKSD
244
P08515
2
217
99.1%
UniRef90_P08515
2
217
secondary structure
beta
5
9
secondary structure
helix
13
24
secondary structure
beta
31
36
secondary structure
helix
41
45
secondary structure
beta
61
63
secondary structure
beta
68
70
secondary structure
helix
72
73
secondary structure
helix
75
83
secondary structure
helix
91
112
secondary structure
helix
120
141
secondary structure
beta
148
148
secondary structure
beta
151
151
secondary structure
helix
156
163
secondary structure
helix
165
172
secondary structure
helix
181
191
secondary structure
helix
194
200
pfam
PF02798.17
GST_N
3
77
pfam
PF14497.3
GST_C_3
100
196
Data of the urea- and temperature-induced unfolding of the dimer indicate the absence of thermodynamically stable intermediates and that the unfolding/refolding transition is a two-state process involving folded native dimer and unfolded monomer. Thermograms obtained by differential scanning microcalorimetry also fitted a two-state unfolding transition model (PMID:9041642).
1b8x
1bg5
1dug
1gne
1gta
1gtb
1m99
1m9a
1m9b
1u87
1u88
1ua5
1y6e
3crt
3cru
3d0z
3qmz
4ai6
4akg
4akh
4aki
4ecb
4ecc
4wr5
5gzz
MF2210014
Monellin
1krl
X-ray
1.90
heterodimer
Dioscoreophyllum cumminsii
9878408
Hung LW, Kohmura M, Ariyoshi Y, Kim SH
Structural differences in D and L-monellin in the crystals of racemic mixture.
J. Mol. Biol.
1999
1
285
311-21
The racemic mixture of synthetic d and l-monellin has been crystallized, and its structure has been determined by X-ray crystallography at 1.9 A resolution. The crystal structure consists of two d and two l-monellin molecules in the P1 unit cell with a pseudo-centrosymmetrical arrangement. The final structure reveals small but significant structural differences between d and l-monellin in the same crystal. Possible reasons for these differences and their implications are discussed.
Chains C and D were removed as chains A and B represent the biologically active dimer.
2
2
Other
Other
A
Monellin chain A
Dioscoreophyllum cumminsii
REIKGYEYQLYVYASDKLFRADISEDYKTRGRKLLRFNGPVPPP
44
P02881
2
45
97.8%
UniRef90_P02881
2
45
secondary structure
beta
6
15
secondary structure
beta
18
27
secondary structure
beta
33
39
pfam
PF09200.7
Monellin
2
44
B
Monellin chain B
Dioscoreophyllum cumminsii
GEWEIIDIGPFTQNLGKFAVDEENKIGQYGRLTFNKVIRPCMKKTIYEEN
50
P02882
1
50
100%
UniRef90_P02882
1
50
secondary structure
beta
3
6
secondary structure
helix
10
26
secondary structure
beta
34
46
pfam
PF09200.7
Monellin
1
40
The two chains of monellin have been shown to be unstructured prior to assembly of the dimer. While the native dimeric structure is reached through various competing pathways entailing different intermediates, these partially structured states can only arise after the encounter complex has been formed (PMID:22542529).
3mon
4mon
3pxm
3pyj
3q2p
5lc6
5lc7
MF2120027
Bacterial antitoxin CcdA
2adl
NMR
homodimer
Escherichia coli
17007877
Madl T, Van Melderen L, Mine N, Respondek M, Oberer M, Keller W, Khatai L, Zangger K
Structural basis for nucleic acid and toxin recognition of the bacterial antitoxin CcdA.
J. Mol. Biol.
2006
2
364
170-85
Toxin-antitoxin systems are highly abundant in plasmids and bacterial chromosomes. They ensure plasmid maintenance by killing bacteria that have lost the plasmid. Their expression is autoregulated at the level of transcription. Here, we present the solution structure of CcdA, the antitoxin of the ccd system, as a free protein (16.7 kDa) and in complex with its cognate DNA (25.3 kDa). CcdA is composed of two distinct and independent domains: the N-terminal domain, responsible for DNA binding, which establishes a new family of the ribbon-helix-helix fold and the C-terminal region, which is responsible for the interaction with the toxin CcdB. The C-terminal domain is intrinsically unstructured and forms a tight complex with the toxin. We show that CcdA specifically recognizes a 6 bp palindromic DNA sequence within the operator-promoter (OP) region of the ccd operon and binds to DNA by insertion of the positively charged N-terminal beta-sheet into the major groove. The binding of up to three CcdA dimers to a 33mer DNA of its operator-promoter region was studied by NMR spectroscopy, isothermal titration calorimetry and single point mutation. The highly flexible C-terminal region of free CcdA explains its susceptibility to proteolysis by the Lon ATP-dependent protease.
GO:0003677
DNA binding
GO:0006355
regulation of transcription, DNA-templated
GO:0006351
transcription, DNA-templated
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Other
Ribbon-helix-helix (RHH)
A
Antitoxin CcdA
Escherichia coli
MKQRITVTVDSDSYQLLKAYDVNISGLVSTTMQNEARRLRAERWKVENQEGMVEVARFIEMNGSFADENKDW
72
P62552
1
72
100%
UniRef90_P62553
1
72
secondary structure
beta
4
8
secondary structure
helix
14
19
secondary structure
helix
25
38
pfam
PF07362.9
CcdA
2
72
B
Antitoxin CcdA
Escherichia coli
MKQRITVTVDSDSYQLLKAYDVNISGLVSTTMQNEARRLRAERWKVENQEGMVEVARFIEMNGSFADENKDW
72
P62552
1
72
100%
UniRef90_P62553
1
72
secondary structure
beta
4
8
secondary structure
helix
14
18
secondary structure
helix
25
38
pfam
PF07362.9
CcdA
2
72
The interacting chains form a ribbon-helix-helix (RHH) structure (PMID:17007877). These structures in general have been described with the two monomers adopting a stable conformation upon the interaction (PMID:17676053). The hydrophobic core stabilizing the complex is formed by both interactors and is thus absent prior to the interaction (PMID:25713077).
2adn
2h3a
2h3c
3g7z
3hpw
3tcj
MF6110001
Nucleoside diphosphate kinase (Dictyostelium discoideum)
1npk
X-ray
1.80
homohexamer
Dictyostelium discoideum
7966307
Moréra S, LeBras G, Lascu I, Lacombe ML, Véron M, Janin J
Refined X-ray structure of Dictyostelium discoideum nucleoside diphosphate kinase at 1.8 A resolution.
J. Mol. Biol.
1994
5
243
873-90
The X-ray structure of the nucleoside diphosphate kinase (NDP kinase) from Dictyostelium discoideum has been refined at 1.8 A resolution from a hexagonal crystal form with a 17 kDa monomer in its asymmetric unit. The atomic model was derived from the previously determined structure of a point mutant of the protein. It contains 150 amino acid residues out of 155, and 95 solvent molecules. The R-factor is 0.196 and the estimated accuracy of the average atomic position, 0.25 A. The Dictyostelium structure is described in detail and compared to those of Drosophila and Myxococcus xanthus NDP kinases. The protein is a hexamer with D3 symmetry. Residues 8 to 138 of each subunit form a globular alpha/beta domain. The four-stranded beta-sheet is antiparallel; its topology is different from other phosphate transfer enzymes, and also from the HPr protein which, like NDP kinase, carries a phosphorylated histidine. The same topology is nevertheless found in several other proteins that bind mononucleotides, RNA or DNA. Strand connections in NDP kinase involve alpha-helices and a 20-residue segment called the Kpn loop. The beta-sheet is regular except for a beta-bulge in edge strand beta 2 and a gamma-turn at residue Ile120 just preceding strand beta 4. The latter may induce strain in the main chain near the active site His122. The alpha 1 beta 2 motif participates in forming dimers within the hexamer, helices alpha 1 and alpha 3, the Kpn loop and C terminus, in forming trimers. The subunit fold and dimer interactions found in Dictyostelium are conserved in other NDP kinases. Trimer interactions probably occur in all eukaryotic enzymes. They are absent in the bacterial Myxococcus xanthus enzyme which is a tetramer, even though the subunit structure is very similar. In Dictyostelium, contacts between Kpn loops near the 3-fold axis block access to a central cavity lined with polar residues and filled with well-defined solvent molecules. Biochemical data on point mutants highlight the contribution of the Kpn loop to protein stability. In Myxococcus, the Kpn loops are on the tetramer surface and their sequence is poorly conserved. Yet, their conformation is maintained and they make a similar contribution to the substrate binding site.
GO:0005524
ATP binding
GO:0004550
nucleoside diphosphate kinase activity
GO:0046872
metal ion binding
GO:0006414
translational elongation
GO:0009617
response to bacterium
GO:0007186
G-protein coupled receptor signaling pathway
GO:0048550
negative regulation of pinocytosis
GO:0006187
dGTP biosynthetic process from dGDP
GO:0006228
UTP biosynthetic process
GO:0006183
GTP biosynthetic process
GO:0006241
CTP biosynthetic process
GO:0045920
negative regulation of exocytosis
GO:0006186
dGDP phosphorylation
GO:0016049
cell growth
GO:0050765
negative regulation of phagocytosis
GO:0030036
actin cytoskeleton organization
GO:0005840
ribosome
GO:0030141
secretory granule
GO:0005856
cytoskeleton
GO:0045335
phagocytic vesicle
GO:0005886
plasma membrane
Chains B, C, D, E and F were generated from chain A using the biomatrices described in the original PDB file.
6
1
Homooligomeric enzymes
Homohexameric enzymes
A
Nucleoside diphosphate kinase, cytosolic
Dictyostelium discoideum
STNKVNKERTFLAVKPDGVARGLVGEIIARYEKKGFVLVGLKQLVPTKDLAESHYAEHKERPFFGGLVSFITSGPVVAMVFEGKGVVASARLMIGVTNPLASAPGSIRGDFGVDVGRNIIHGSDSVESANREIALWFKPEELLTEVKPNPNLYE
154
P22887
2
155
99.4%
UniRef90_P22887
2
155
secondary structure
beta
10
15
secondary structure
helix
17
21
secondary structure
helix
25
35
secondary structure
beta
38
45
secondary structure
helix
49
55
secondary structure
helix
57
59
secondary structure
helix
65
72
secondary structure
beta
77
83
secondary structure
helix
87
95
secondary structure
helix
100
102
secondary structure
helix
108
112
secondary structure
beta
115
115
secondary structure
beta
118
118
secondary structure
beta
121
123
secondary structure
helix
127
137
secondary structure
helix
140
142
pfam
PF00334.16
NDK
9
143
B
Nucleoside diphosphate kinase, cytosolic
Dictyostelium discoideum
STNKVNKERTFLAVKPDGVARGLVGEIIARYEKKGFVLVGLKQLVPTKDLAESHYAEHKERPFFGGLVSFITSGPVVAMVFEGKGVVASARLMIGVTNPLASAPGSIRGDFGVDVGRNIIHGSDSVESANREIALWFKPEELLTEVKPNPNLYE
154
P22887
2
155
99.4%
UniRef90_P22887
2
155
secondary structure
beta
10
15
secondary structure
helix
17
21
secondary structure
helix
25
35
secondary structure
beta
38
45
secondary structure
helix
49
55
secondary structure
helix
57
59
secondary structure
helix
65
72
secondary structure
beta
77
83
secondary structure
helix
87
95
secondary structure
helix
100
102
secondary structure
helix
108
112
secondary structure
beta
115
115
secondary structure
beta
118
118
secondary structure
beta
121
123
secondary structure
helix
127
137
secondary structure
helix
140
142
pfam
PF00334.16
NDK
9
143
C
Nucleoside diphosphate kinase, cytosolic
Dictyostelium discoideum
STNKVNKERTFLAVKPDGVARGLVGEIIARYEKKGFVLVGLKQLVPTKDLAESHYAEHKERPFFGGLVSFITSGPVVAMVFEGKGVVASARLMIGVTNPLASAPGSIRGDFGVDVGRNIIHGSDSVESANREIALWFKPEELLTEVKPNPNLYE
154
P22887
2
155
99.4%
UniRef90_P22887
2
155
secondary structure
beta
10
15
secondary structure
helix
17
21
secondary structure
helix
25
35
secondary structure
beta
38
45
secondary structure
helix
49
55
secondary structure
helix
57
59
secondary structure
helix
65
72
secondary structure
beta
77
83
secondary structure
helix
87
95
secondary structure
helix
100
102
secondary structure
helix
108
112
secondary structure
beta
115
115
secondary structure
beta
118
118
secondary structure
beta
121
123
secondary structure
helix
127
137
secondary structure
helix
140
142
pfam
PF00334.16
NDK
9
143
D
Nucleoside diphosphate kinase, cytosolic
Dictyostelium discoideum
STNKVNKERTFLAVKPDGVARGLVGEIIARYEKKGFVLVGLKQLVPTKDLAESHYAEHKERPFFGGLVSFITSGPVVAMVFEGKGVVASARLMIGVTNPLASAPGSIRGDFGVDVGRNIIHGSDSVESANREIALWFKPEELLTEVKPNPNLYE
154
P22887
2
155
99.4%
UniRef90_P22887
2
155
secondary structure
beta
10
15
secondary structure
helix
17
21
secondary structure
helix
25
35
secondary structure
beta
38
45
secondary structure
helix
49
55
secondary structure
helix
57
59
secondary structure
helix
65
72
secondary structure
beta
77
83
secondary structure
helix
87
95
secondary structure
helix
100
102
secondary structure
helix
108
112
secondary structure
beta
115
115
secondary structure
beta
118
118
secondary structure
beta
121
123
secondary structure
helix
127
137
secondary structure
helix
140
142
pfam
PF00334.16
NDK
9
143
E
Nucleoside diphosphate kinase, cytosolic
Dictyostelium discoideum
STNKVNKERTFLAVKPDGVARGLVGEIIARYEKKGFVLVGLKQLVPTKDLAESHYAEHKERPFFGGLVSFITSGPVVAMVFEGKGVVASARLMIGVTNPLASAPGSIRGDFGVDVGRNIIHGSDSVESANREIALWFKPEELLTEVKPNPNLYE
154
P22887
2
155
99.4%
UniRef90_P22887
2
155
secondary structure
beta
10
15
secondary structure
helix
17
21
secondary structure
helix
25
35
secondary structure
beta
38
45
secondary structure
helix
49
55
secondary structure
helix
57
59
secondary structure
helix
65
72
secondary structure
beta
77
83
secondary structure
helix
87
95
secondary structure
helix
100
102
secondary structure
helix
108
112
secondary structure
beta
115
115
secondary structure
beta
118
118
secondary structure
beta
121
123
secondary structure
helix
127
137
secondary structure
helix
140
142
pfam
PF00334.16
NDK
9
143
F
Nucleoside diphosphate kinase, cytosolic
Dictyostelium discoideum
STNKVNKERTFLAVKPDGVARGLVGEIIARYEKKGFVLVGLKQLVPTKDLAESHYAEHKERPFFGGLVSFITSGPVVAMVFEGKGVVASARLMIGVTNPLASAPGSIRGDFGVDVGRNIIHGSDSVESANREIALWFKPEELLTEVKPNPNLYE
154
P22887
2
155
99.4%
UniRef90_P22887
2
155
secondary structure
beta
10
15
secondary structure
helix
17
21
secondary structure
helix
25
35
secondary structure
beta
38
45
secondary structure
helix
49
55
secondary structure
helix
57
59
secondary structure
helix
65
72
secondary structure
beta
77
83
secondary structure
helix
87
95
secondary structure
helix
100
102
secondary structure
helix
108
112
secondary structure
beta
115
115
secondary structure
beta
118
118
secondary structure
beta
121
123
secondary structure
helix
127
137
secondary structure
helix
140
142
pfam
PF00334.16
NDK
9
143
The hexameric NDP kinase from Dictyostelium discoideum displays one single, irreversible differential scanning calorimetry peak (Tm=62°C) over a broad protein concentration, indicating a single step denaturation. However, the P105G substitution, which affects a loop implicated in subunit contacts, yields a protein that reversibly dissociates to folded monomers at 38°C before the irreversible denaturation occurs (Tm=47°C). These data indicate a âcouplingâ of the quaternary structure with the tertiary structure in the wild-type, but not in the mutated protein (PMID:8663370).
1b4s
1b99
1bux
1f3f
1f6t
1hhq
1hiy
1hlw
1kdn
1leo
1lwx
1mn7
1mn9
1ncl
1ndc
1ndk
1ndp
1nsp
1pae
1s5z
2bef
3fkb
4c6a
4cp5
MF2100014
Superoxide dismutase (SOD)
2c9v
X-ray
1.07
homodimer
Homo sapiens
16406071
Strange RW, Antonyuk SV, Hough MA, Doucette PA, Valentine JS, Hasnain SS
Variable metallation of human superoxide dismutase: atomic resolution crystal structures of Cu-Zn, Zn-Zn and as-isolated wild-type enzymes.
J. Mol. Biol.
2006
5
356
1152-62
Human Cu-Zn superoxide dismutase (SOD1) protects cells from the effects of oxidative stress. Mutations in SOD1 are linked to the familial form of amyotrophic lateral sclerosis. Several hypotheses for their toxicity involve the mis-metallation of the enzyme. We present atomic-resolution crystal structures and biophysical data for human SOD1 in three metallation states: Zn-Zn, Cu-Zn and as-isolated. These data represent the first atomic-resolution structures for human SOD1, the first structure of a reduced SOD1, and the first structure of a fully Zn-substituted SOD1 enzyme. Recombinantly expressed as-isolated SOD1 contains a mixture of Zn and Cu at the Cu-binding site. The Zn-Zn structure appears to be at least as stable as the correctly (Cu-Zn) metallated enzyme. These data raise the possibility that in a cellular environment with low availability of free copper, Zn-Zn may be the preferred metallation state of SOD1 prior to its interaction with the copper chaperone.
GO:0004784
superoxide dismutase activity
GO:0008270
zinc ion binding
GO:0051087
chaperone binding
GO:0042803
protein homodimerization activity
GO:0030346
protein phosphatase 2B binding
GO:0005507
copper ion binding
GO:0048365
Rac GTPase binding
GO:0046688
response to copper ion
GO:0007605
sensory perception of sound
GO:0001890
placenta development
GO:0043087
regulation of GTPase activity
GO:0071318
cellular response to ATP
GO:0000187
activation of MAPK activity
GO:0048678
response to axon injury
GO:0045471
response to ethanol
GO:0050665
hydrogen peroxide biosynthetic process
GO:0032287
peripheral nervous system myelin maintenance
GO:0060052
neurofilament cytoskeleton organization
GO:0034465
response to carbon monoxide
GO:0040014
regulation of multicellular organism growth
GO:0006879
cellular iron ion homeostasis
GO:0046677
response to antibiotic
GO:0008217
regulation of blood pressure
GO:0032930
positive regulation of superoxide anion generation
GO:0046620
regulation of organ growth
GO:0001895
retina homeostasis
GO:0007283
spermatogenesis
GO:0008089
anterograde axonal transport
GO:0007569
cell aging
GO:0035865
cellular response to potassium ion
GO:0007566
embryo implantation
GO:0060047
heart contraction
GO:0060088
auditory receptor cell stereocilium organization
GO:0051881
regulation of mitochondrial membrane potential
GO:0002262
myeloid cell homeostasis
GO:0009408
response to heat
GO:0001975
response to amphetamine
GO:0006749
glutathione metabolic process
GO:0033081
regulation of T cell differentiation in thymus
GO:0060087
relaxation of vascular smooth muscle
GO:0055114
oxidation-reduction process
GO:0001541
ovarian follicle development
GO:0043524
negative regulation of neuron apoptotic process
GO:0097332
response to antipsychotic drug
GO:0019430
removal of superoxide radicals
GO:1902177
positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
GO:0007626
locomotory behavior
GO:0046716
muscle cell cellular homeostasis
GO:0019226
transmission of nerve impulse
GO:0002576
platelet degranulation
GO:0071276
cellular response to cadmium ion
GO:0048538
thymus development
GO:0008090
retrograde axonal transport
GO:0042554
superoxide anion generation
GO:0042542
response to hydrogen peroxide
GO:0001819
positive regulation of cytokine production
GO:0031667
response to nutrient levels
GO:0045541
negative regulation of cholesterol biosynthetic process
GO:1904115
axon cytoplasm
GO:0031012
extracellular matrix
GO:0005829
cytosol
GO:0032839
dendrite cytoplasm
GO:0043234
protein complex
GO:0005777
peroxisome
GO:0005654
nucleoplasm
GO:0043209
myelin sheath
GO:0005758
mitochondrial intermembrane space
GO:0005764
lysosome
GO:0005759
mitochondrial matrix
GO:0070062
extracellular exosome
GO:0005615
extracellular space
GO:0031045
dense core granule
GO:0043025
neuronal cell body
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Homooligomeric enzymes
Homodimeric enzymes
A
Superoxide dismutase [Cu-Zn]
Homo sapiens
ATKAVCVLKGDGPVQGIINFEQKESNGPVKVWGSIKGLTEGLHGFHVHEFGDNTAGCTSAGPHFNPLSRKHGGPKDEERHVGDLGNVTADKDGVADVSIEDSVISLSGDHCIIGRTLVVHEKADDLGKGGNEESTKTGNAGSRLACGVIGIAQ
153
P00441
2
154
99.4%
UniRef90_P00441
2
154
secondary structure
beta
3
10
secondary structure
beta
16
23
secondary structure
beta
30
37
secondary structure
beta
42
49
secondary structure
helix
57
61
secondary structure
beta
64
64
secondary structure
beta
84
90
secondary structure
beta
96
102
secondary structure
beta
106
106
secondary structure
helix
109
111
secondary structure
beta
112
112
secondary structure
beta
117
121
secondary structure
helix
133
136
secondary structure
beta
144
149
secondary structure
beta
151
152
pfam
PF00080.17
Sod_Cu
9
150
F
Superoxide dismutase [Cu-Zn]
Homo sapiens
ATKAVCVLKGDGPVQGIINFEQKESNGPVKVWGSIKGLTEGLHGFHVHEFGDNTAGCTSAGPHFNPLSRKHGGPKDEERHVGDLGNVTADKDGVADVSIEDSVISLSGDHCIIGRTLVVHEKADDLGKGGNEESTKTGNAGSRLACGVIGIAQ
153
P00441
2
154
99.4%
UniRef90_P00441
2
154
secondary structure
beta
4
11
secondary structure
beta
15
23
secondary structure
beta
30
37
secondary structure
beta
42
49
secondary structure
helix
57
61
secondary structure
beta
64
64
secondary structure
beta
84
90
secondary structure
beta
96
102
secondary structure
beta
106
106
secondary structure
beta
112
112
secondary structure
beta
117
121
secondary structure
helix
135
138
secondary structure
beta
144
149
secondary structure
beta
151
152
pfam
PF00080.17
Sod_Cu
9
150
CD measurements and a global analysis decomposition of the time-resolved fluorescence decay over denaturant concentration shows the presence of an intermediate in the unfolding of human SOD by guanidinium hydrochloride. Considering previous measurements of partially denatured HSOD as a function of protein concentration (PMID:1510915), these results strongly suggest that the unfolding intermediate is a monomer that displays a molten globule state (PMID:8298055).
1azv
1ba9
1dsw
1fun
1hl4
1hl5
1kmg
1l3n
1mfm
1n18
1n19
1oez
1ozt
1ozu
1p1v
1ptz
1pu0
1rk7
1sos
1spd
1uxl
1uxm
2af2
2c9s
2c9u
2gbt
2gbu
2gbv
2lu5
2mp3
2nnx
2r27
2v0a
2vr6
2vr7
2vr8
2wko
2wyt
2wyz
2wz0
2wz5
2wz6
2xjk
2xjl
2zkw
2zkx
2zky
3cqp
3cqq
3ecu
3ecv
3ecw
3gqf
3gtv
3gzo
3gzp
3gzq
3h2p
3h2q
3hff
3k91
3kh3
3kh4
3ltv
3qqd
3re0
3t5w
4a7g
4a7q
4a7s
4a7t
4a7u
4a7v
4b3e
4bcy
4bcz
4bd4
4ff9
4mcm
4mcn
4nin
4nio
4nip
4oh2
4sod
4xcr
5dli
2nam
5j0f
5j0g
5k02
MF2120028
Subtilisin inhibitor (SSI)
3ssi
X-ray
2.30
homodimer
Streptomyces albogriseolus
Suzuki, T.
Structural Modulation of the Protein Proteinase Inhibitor Ssi (Streptomyces Subtilisin Inhibitor)
To be published
-
GO:0004867
serine-type endopeptidase inhibitor activity
GO:0010951
negative regulation of endopeptidase activity
GO:0005576
extracellular region
Chain B was generated from chain A using the biomatrix described in the original PDB file.
2
1
Other
Other
A
Subtilisin inhibitor
Streptomyces albogriseolus
DAPSALYAPSALVLTVGKGVSATTAAPERAVTLTCAPGPSGTHPAAGSACADLAAVGGDLNALTRGEDVMCPMVYDPVLLTVDGVWQGKRVSYERVFSNECEMNAHGSSVFAF
113
P01006
32
144
78.5%
UniRef90_P01006
32
144
secondary structure
beta
42
49
secondary structure
beta
60
65
secondary structure
beta
71
71
secondary structure
helix
77
86
secondary structure
helix
91
93
secondary structure
beta
96
96
secondary structure
beta
109
117
secondary structure
beta
120
128
secondary structure
helix
131
134
secondary structure
beta
137
137
pfam
PF00720.14
SSI
39
130
B
Subtilisin inhibitor
Streptomyces albogriseolus
DAPSALYAPSALVLTVGKGVSATTAAPERAVTLTCAPGPSGTHPAAGSACADLAAVGGDLNALTRGEDVMCPMVYDPVLLTVDGVWQGKRVSYERVFSNECEMNAHGSSVFAF
113
P01006
32
144
78.5%
UniRef90_P01006
32
144
secondary structure
beta
42
49
secondary structure
beta
60
65
secondary structure
beta
71
71
secondary structure
helix
77
86
secondary structure
helix
91
93
secondary structure
beta
96
96
secondary structure
beta
109
117
secondary structure
beta
120
128
secondary structure
helix
131
134
secondary structure
beta
137
137
pfam
PF00720.14
SSI
39
130
The thermal unfolding of SSI has been studied by differential scanning calorimetry (DSC). The DSC data show that dimeric SSI remains dimeric as the temperature is raised until it unfolds and that it then dissociates during the unfolding process (PMID:7030385).
2sic
3sic
5sic
MF2110019
4-aminobutyrate aminotransferase
1ohv
X-ray
2.30
homodimer
Sus scrofa
14534310
Storici P, De Biase D, Bossa F, Bruno S, Mozzarelli A, Peneff C, Silverman RB, Schirmer T
Structures of gamma-aminobutyric acid (GABA) aminotransferase, a pyridoxal 5'-phosphate, and [2Fe-2S] cluster-containing enzyme, complexed with gamma-ethynyl-GABA and with the antiepilepsy drug vigabatrin.
J. Biol. Chem.
2004
1
279
363-73
Gamma-aminobutyric acid aminotransferase (GABA-AT) is a pyridoxal 5'-phosphate-dependent enzyme responsible for the degradation of the inhibitory neurotransmitter GABA. GABA-AT is a validated target for antiepilepsy drugs because its selective inhibition raises GABA concentrations in brain. The antiepilepsy drug, gamma-vinyl-GABA (vigabatrin) has been investigated in the past by various biochemical methods and resulted in several proposals for its mechanisms of inactivation. In this study we solved and compared the crystal structures of pig liver GABA-AT in its native form (to 2.3-A resolution) and in complex with vigabatrin as well as with the close analogue gamma-ethynyl-GABA (to 2.3 and 2.8 A, respectively). Both inactivators form a covalent ternary adduct with the active site Lys-329 and the pyridoxal 5'-phosphate (PLP) cofactor. The crystal structures provide direct support for specific inactivation mechanisms proposed earlier on the basis of radio-labeling experiments. The reactivity of GABA-AT crystals with the two GABA analogues was also investigated by polarized absorption microspectrophotometry. The spectral data are discussed in relation to the proposed mechanism. Intriguingly, all three structures revealed a [2Fe-2S] cluster of yet unknown function at the center of the dimeric molecule in the vicinity of the PLP cofactors.
GO:0032145
succinate-semialdehyde dehydrogenase binding
GO:0003867
4-aminobutyrate transaminase activity
GO:0051537
2 iron, 2 sulfur cluster binding
GO:0030170
pyridoxal phosphate binding
GO:0046872
metal ion binding
GO:0047298
(S)-3-amino-2-methylpropionate transaminase activity
GO:0042803
protein homodimerization activity
GO:0042135
neurotransmitter catabolic process
GO:0048148
behavioral response to cocaine
GO:0009450
gamma-aminobutyric acid catabolic process
GO:0005759
mitochondrial matrix
GO:0005829
cytosol
GO:0032144
4-aminobutyrate transaminase complex
Chains C and D were removed as chains A and B represent the biologically active dimer.
2
1
Homooligomeric enzymes
Homodimeric enzymes
A
4-aminobutyrate aminotransferase, mitochondrial
Sus scrofa
SQAAAKVDVEFDYDGPLMKTEVPGPRSRELMKQLNIIQNAEAVHFFCNYEESRGNYLVDVDGNRMLDLYSQISSIPIGYSHPALVKLVQQPQNVSTFINRPALGILPPENFVEKLRESLLSVAPKGMSQLITMACGSCSNENAFKTIFMWYRSKERGQSAFSKEELETCMINQAPGCPDYSILSFMGAFHGRTMGCLATTHSKAIHKIDIPSFDWPIAPFPRLKYPLEEFVKENQQEEARCLEEVEDLIVKYRKKKKTVAGIIVEPIQSEGGDNHASDDFFRKLRDISRKHGCAFLVDEVQTGGGSTGKFWAHEHWGLDDPADVMTFSKKMMTGGFFHKEEFRPNAPYRIFNTWLGDPSKNLLLAEVINIIKREDLLSNAAHAGKVLLTGLLDLQARYPQFISRVRGRGTFCSFDTPDESIRNKLISIARNKGVMLGGCGDKSIRFRPTLVFRDHHAHLFLNIFSDILADFK
472
P80147
39
499
92.2%
UniRef90_P80147
39
499
secondary structure
beta
45
45
secondary structure
helix
53
65
secondary structure
beta
75
75
secondary structure
helix
77
79
secondary structure
beta
81
82
secondary structure
beta
84
87
secondary structure
beta
92
95
secondary structure
helix
98
101
secondary structure
beta
107
107
secondary structure
helix
110
117
secondary structure
helix
119
126
secondary structure
beta
136
136
secondary structure
helix
139
145
secondary structure
helix
147
150
secondary structure
beta
157
161
secondary structure
helix
164
184
secondary structure
helix
191
198
secondary structure
beta
209
213
secondary structure
helix
222
227
secondary structure
helix
232
235
secondary structure
beta
245
246
secondary structure
helix
255
257
secondary structure
helix
259
282
secondary structure
beta
287
292
secondary structure
beta
296
296
secondary structure
beta
302
302
secondary structure
helix
306
318
secondary structure
beta
322
326
secondary structure
helix
340
344
secondary structure
beta
352
355
secondary structure
helix
357
359
secondary structure
beta
362
366
secondary structure
helix
368
370
secondary structure
helix
386
401
secondary structure
helix
404
425
secondary structure
beta
431
436
secondary structure
beta
439
443
secondary structure
helix
447
459
secondary structure
beta
462
463
secondary structure
beta
465
467
secondary structure
beta
471
474
secondary structure
helix
482
497
pfam
PF00202.18
Aminotran_3
65
496
B
4-aminobutyrate aminotransferase, mitochondrial
Sus scrofa
SQAAAKVDVEFDYDGPLMKTEVPGPRSRELMKQLNIIQNAEAVHFFCNYEESRGNYLVDVDGNRMLDLYSQISSIPIGYSHPALVKLVQQPQNVSTFINRPALGILPPENFVEKLRESLLSVAPKGMSQLITMACGSCSNENAFKTIFMWYRSKERGQSAFSKEELETCMINQAPGCPDYSILSFMGAFHGRTMGCLATTHSKAIHKIDIPSFDWPIAPFPRLKYPLEEFVKENQQEEARCLEEVEDLIVKYRKKKKTVAGIIVEPIQSEGGDNHASDDFFRKLRDISRKHGCAFLVDEVQTGGGSTGKFWAHEHWGLDDPADVMTFSKKMMTGGFFHKEEFRPNAPYRIFNTWLGDPSKNLLLAEVINIIKREDLLSNAAHAGKVLLTGLLDLQARYPQFISRVRGRGTFCSFDTPDESIRNKLISIARNKGVMLGGCGDKSIRFRPTLVFRDHHAHLFLNIFSDILADFK
472
P80147
39
499
92.2%
UniRef90_P80147
39
499
secondary structure
beta
45
45
secondary structure
helix
53
65
secondary structure
beta
75
75
secondary structure
beta
81
82
secondary structure
beta
84
87
secondary structure
beta
92
95
secondary structure
helix
98
101
secondary structure
beta
107
107
secondary structure
helix
110
117
secondary structure
helix
119
126
secondary structure
beta
136
136
secondary structure
helix
139
145
secondary structure
helix
147
150
secondary structure
beta
157
161
secondary structure
helix
164
184
secondary structure
helix
191
198
secondary structure
beta
209
213
secondary structure
helix
222
227
secondary structure
helix
232
235
secondary structure
beta
245
246
secondary structure
helix
255
257
secondary structure
helix
259
282
secondary structure
beta
287
292
secondary structure
beta
296
296
secondary structure
beta
302
302
secondary structure
helix
306
318
secondary structure
beta
322
326
secondary structure
helix
340
344
secondary structure
beta
352
355
secondary structure
helix
357
359
secondary structure
beta
362
366
secondary structure
helix
368
370
secondary structure
helix
386
401
secondary structure
helix
404
425
secondary structure
beta
431
436
secondary structure
beta
439
443
secondary structure
helix
447
459
secondary structure
beta
462
463
secondary structure
beta
465
467
secondary structure
beta
471
473
secondary structure
helix
482
497
pfam
PF00202.18
Aminotran_3
65
496
The unfolding of pig liver 4-aminobutyrate aminotransferase by urea has been investigated at equilibrium. Unfolding of the enzyme was monitored by circular dichroism and fluorescence spectroscopy. The steepness of the fluorescence and CD changes between 2 and 8 M urea, and the lack of any discernible plateau suggests that unfolding of the protein is a cooperative process. The unfolding of 4-aminobutyrate aminotransferase as a function of urea concentration was monitored by fluorescence measurements of the tryptophanyl residues. The kinetic results indicate that the aminotransferase unfolds in a single kinetic phase (PMID:8075151).
1ohw
1ohy
4y0d
4y0h
4y0i
4zsw
4zsy
MF2140011
Dimeric Mnt repressor
1mnt
NMR
homodimer
Enterobacteria phage P22
7999761
Burgering MJ, Boelens R, Gilbert DE, Breg JN, Knight KL, Sauer RT, Kaptein R
Solution structure of dimeric Mnt repressor (1-76).
Biochemistry
1994
50
33
15036-45
Wild-type Mnt repressor of Salmonella bacteriophage P22 is a tetrameric protein of 82 residues per monomer. A C-terminal deletion mutant of the repressor denoted Mnt (1-76) is a dimer in solution. The structure of this dimer has been determined using NMR. The NMR assignments of the majority of the 1H, 15N, and 13C resonances were obtained using 2D and triple-resonance 3D techniques. Elements of secondary structure were identified on the basis of characteristic sequential and medium range NOEs. For the structure determination more than 1000 NOEs per monomer were obtained, and structures were generated using distance geometry and restrained simulated annealing calculations. The discrimination of intra- vs intermonomer NOEs was based upon the observation of intersubunit NOEs in [15N,13C] double half-filtered NOESY experiments. The N-terminal part of Mnt (residues 1-44), which shows a 40% sequence homology with the Arc repressor, has a similar secondary and tertiary structure. Mnt (1-76) continues with a loop region of irregular structure, a third alpha-helix, and a random coil C-terminal peptide. Analysis of the secondary structure NOEs, the exchange rates, and the backbone chemical shifts suggests that the carboxy-terminal third helix is less stable than the remainder of the protein, but the observation of intersubunit NOEs for this part of the protein enables the positioning of this helix. The rsmd's between the backbone atoms of the N-terminal part of the Mnt repressor (residues 5-43, 5'-43') and the Arc repressor is 1.58 A, and between this region and the corresponding part of the MetJ repressor 1.43 A.
GO:0003677
DNA binding
GO:0006355
regulation of transcription, DNA-templated
GO:0006351
transcription, DNA-templated
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Other
Ribbon-helix-helix (RHH)
A
Regulatory protein mnt
Enterobacteria phage P22
ARDDPHFNFRMPMEVREKLKFRAEANGRSMNSELLQIVQDALSKPSPVTGYRNDAERLADEQSELVKKMVFDTLKD
76
P03049
2
77
91.6%
UniRef90_P03049
2
77
secondary structure
beta
9
11
secondary structure
helix
14
22
secondary structure
helix
24
27
secondary structure
helix
32
44
secondary structure
helix
56
65
pfam
PF03869.11
Arc
2
51
pfam
PF11423.5
Repressor_Mnt
53
80
B
Regulatory protein mnt
Enterobacteria phage P22
ARDDPHFNFRMPMEVREKLKFRAEANGRSMNSELLQIVQDALSKPSPVTGYRNDAERLADEQSELVKKMVFDTLKD
76
P03049
2
77
91.6%
UniRef90_P03049
2
77
secondary structure
beta
7
9
secondary structure
helix
14
28
secondary structure
helix
32
44
secondary structure
helix
56
63
pfam
PF03869.11
Arc
2
51
pfam
PF11423.5
Repressor_Mnt
53
80
The Mnt repressor shows a high degree of sequential and structural similarity with the Arc and MetJ repressors (PMID:7999761). Both of these close homologues of Mnt repressor have been shown to adopt a stable structure only via dimerization (PMID:8110744, PMID:1390748)
MF2140012
Dimeric serine proteinase from Semliki Forest virus core protein
1vcq
X-ray
3.10
homodimer
Semliki forest virus
9094737
Choi HK, Lu G, Lee S, Wengler G, Rossmann MG
Structure of Semliki Forest virus core protein.
Proteins
1997
3
27
345-59
Alphaviruses are enveloped, insect-borne viruses, which contains a positive-sense RNA genome. The protein capsid is surrounded by a lipid membrane, which is penetrated by glycoprotein spikes. The structure of the Sindbis virus (SINV) (the type virus) core protein (SCP) was previously determined and found to have a chymotrypsin-like structure. SCP is a serine proteinase which cleaves itself from a polyprotein. Semliki Forest virus (SFV) is among the most distantly related alphaviruses to SINV. Similar to SCP, autocatalysis is inhibited in SFCP after cleavage of the polyprotein by leaving the carboxy-terminal tryptophan in the specificity pocket. The structures of two different crystal forms (I and II) of SFV core protein (SFCP) have been determined to 3.0 A and 3.3 A resolution, respectively. The SFCP monomer backbone structure is very similar to that of SCP. The dimeric association between monomers, A and B, found in two different crystal forms of SCP is also present in both crystal forms of SFCP. However, a third monomer, C, occurs in SFCP crystal form I. While monomers A and B make a tail-to-tail dimer contact, monomers B and C make a head-to-head dimer contact. A hydrophobic pocket on the surface of the capsid protein, the proposed site of binding of the E2 glycoprotein, has large conformational differences with respect to SCP and, in contrast to SCP, is found devoid of bound peptide. In particular, Tyr184 is pointing out of the hydrophobic pocket in SFCP, whereas the equivalent tyrosine in SCP is pointing into the pocket. The conformation of Tyr184, found in SFCP, is consistent with its availability for iodination, as observed in the homologous SINV cores. This suggests, by comparison with SCP, that E2 binding to cores causes major conformational changes, including the burial of Tyr184, which would stabilize the intact virus on budding from an infected cell. The head-to-tail contacts found in the pentameric and hexameric associations within the virion utilize in the same monomer surface regions as found in the crystalline dimer interfaces.
GO:0046983
protein dimerization activity
GO:0004252
serine-type endopeptidase activity
GO:0005198
structural molecule activity
GO:0039654
fusion of virus membrane with host endosome membrane
GO:0006508
proteolysis
GO:0019068
virion assembly
GO:0075512
clathrin-mediated endocytosis of virus by host cell
GO:0019062
virion attachment to host cell
GO:0039619
T=4 icosahedral viral capsid
GO:0019031
viral envelope
GO:0055036
virion membrane
GO:0020002
host cell plasma membrane
GO:0044174
host cell endosome
GO:0016021
integral component of membrane
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Homooligomeric enzymes
Homodimeric enzymes
A
Structural polyprotein
Semliki forest virus
CIFEVKHEGKVTGYACLVGDKVMKPAHVKGVIDNADLAKLAFKKSSKYDLECAQIPVHMRSDASKYTHEKPEGHYNWHHGAVQYSGGRFTIPTGAGKPGDSGRPIFDNKGRVVAIVLGGANEGSRTALSVVTWNKDMVTRVTPEGSEEW
149
P03315
119
267
11.9%
UniRef90_P03315
119
267
secondary structure
beta
121
125
secondary structure
beta
128
133
secondary structure
beta
135
136
secondary structure
beta
139
140
secondary structure
beta
143
143
secondary structure
beta
149
150
secondary structure
helix
153
156
secondary structure
beta
161
163
secondary structure
beta
168
172
secondary structure
helix
175
180
secondary structure
beta
182
182
secondary structure
beta
184
184
secondary structure
beta
191
195
secondary structure
beta
198
202
secondary structure
beta
207
210
secondary structure
beta
222
224
secondary structure
beta
230
240
secondary structure
beta
243
251
secondary structure
beta
256
259
pfam
PF00944.16
Peptidase_S3
112
268
B
Structural polyprotein
Semliki forest virus
CIFEVKHEGKVTGYACLVGDKVMKPAHVKGVIDNADLAKLAFKKSSKYDLECAQIPVHMRSDASKYTHEKPEGHYNWHHGAVQYSGGRFTIPTGAGKPGDSGRPIFDNKGRVVAIVLGGANEGSRTALSVVTWNKDMVTRVTPEGSEEW
149
P03315
119
267
11.9%
UniRef90_P03315
119
267
secondary structure
beta
121
125
secondary structure
beta
128
133
secondary structure
beta
135
136
secondary structure
beta
139
140
secondary structure
beta
149
150
secondary structure
helix
153
156
secondary structure
beta
163
163
secondary structure
beta
168
168
secondary structure
beta
171
172
secondary structure
helix
175
180
secondary structure
beta
182
182
secondary structure
beta
184
184
secondary structure
beta
191
195
secondary structure
beta
198
202
secondary structure
beta
207
210
secondary structure
beta
222
224
secondary structure
beta
230
240
secondary structure
beta
243
251
secondary structure
beta
256
259
secondary structure
beta
264
264
pfam
PF00944.16
Peptidase_S3
112
268
A
The 119-260 region described in DisProt entry DP00999 covers 95.3% of the sequence present in the structure.
B
The 119-260 region described in DisProt entry DP00999 covers 95.3% of the sequence present in the structure.
1dyl
1vcp
MF2140013
Influenza A NEP M1-binding domain
1pd3
X-ray
2.60
homodimer
Influenza A virus
12970177
Akarsu H, Burmeister WP, Petosa C, Petit I, Müller CW, Ruigrok RW, Baudin F
Crystal structure of the M1 protein-binding domain of the influenza A virus nuclear export protein (NEP/NS2).
EMBO J.
2003
18
22
4646-55
During influenza virus infection, viral ribonucleoproteins (vRNPs) are replicated in the nucleus and must be exported to the cytoplasm before assembling into mature viral particles. Nuclear export is mediated by the cellular protein Crm1 and putatively by the viral protein NEP/NS2. Proteolytic cleavage of NEP defines an N-terminal domain which mediates RanGTP-dependent binding to Crm1 and a C-terminal domain which binds to the viral matrix protein M1. The 2.6 A crystal structure of the C-terminal domain reveals an amphipathic helical hairpin which dimerizes as a four-helix bundle. The NEP-M1 interaction involves two critical epitopes: an exposed tryptophan (Trp78) surrounded by a cluster of glutamate residues on NEP, and the basic nuclear localization signal (NLS) of M1. Implications for vRNP export are discussed.
GO:0005515
protein binding
GO:0006405
RNA export from nucleus
GO:0019072
viral genome packaging
GO:0019083
viral transcription
GO:0019061
uncoating of virus
GO:0019065
receptor-mediated endocytosis of virus by host cell
GO:0019064
fusion of virus membrane with host plasma membrane
GO:0039675
exit of virus from host cell nucleus through nuclear pore
GO:0019062
virion attachment to host cell
GO:0046761
viral budding from plasma membrane
GO:0030666
endocytic vesicle membrane
GO:0042025
host cell nucleus
GO:0005829
cytosol
GO:0005654
nucleoplasm
GO:0031904
endosome lumen
GO:0019012
virion
GO:0005576
extracellular region
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Coils and zippers
Coiled coil (dimeric, forming a 4-helix bundle)
A
Nuclear export protein
Influenza A virus
QNRNGKWREQLGQKFEEIRWLIEEVRHRLKITENSFEQITFMQALQLLLEVEQEIRTF
58
P03508
59
116
47.9%
UniRef90_P03506
59
116
secondary structure
helix
64
85
secondary structure
helix
94
115
pfam
PF00601.16
Flu_NS2
28
121
B
Nuclear export protein
Influenza A virus
QNRNGKWREQLGQKFEEIRWLIEEVRHRLKITENSFEQITFMQALQLLLEVEQEIRTF
58
P03508
59
116
47.9%
UniRef90_P03506
59
116
secondary structure
helix
65
86
secondary structure
helix
94
114
pfam
PF00601.16
Flu_NS2
28
121
A
The 1-121 region described in DisProt entry DP00871 covers 100% of a close homologue of the sequence present in the structure.
B
The 1-121 region described in DisProt entry DP00871 covers 100% of a close homologue of the sequence present in the structure.
MF2120029
SinR dimerization domain
2yal
X-ray
2.27
homodimer
Bacillus subtilis
21708175
Colledge VL, Fogg MJ, Levdikov VM, Leech A, Dodson EJ, Wilkinson AJ
Structure and organisation of SinR, the master regulator of biofilm formation in Bacillus subtilis.
J. Mol. Biol.
2011
3
411
597-613
sinR encodes a tetrameric repressor of genes required for biofilm formation in Bacillus subtilis. sinI, which is transcribed under Spo0A control, encodes a dimeric protein that binds to SinR to form a SinR-SinI heterodimer in which the DNA-binding functions of SinR are abrogated and repression of biofilm genes is relieved. The heterodimer-forming surface comprises residues conserved between SinR and SinI. Each forms a pair of α-helices that hook together to form an intermolecular four-helix bundle. Here, we are interested in the assembly of the SinR tetramer and its binding to DNA. Size-exclusion chromatography with multi-angle laser light scattering and crystallographic analysis reveal that a DNA-binding fragment of SinR (residues 1-69) is a monomer, while a SinI-binding fragment (residues 74-111) is a tetramer arranged as a dimer of dimers. The SinR(74-111) chain forms two α-helices with the organisation of the dimer similar to that observed in the SinR-SinI complex. The tetramer is formed through interactions of residues at the C-termini of the four chains. A model of the intact SinR tetramer in which the DNA binding domains surround the tetramerisation core was built. Fluorescence anisotropy and surface plasmon resonance experiments showed that SinR binds to an oligonucleotide duplex, 5'-TTTGTTCTCTAAAGAGAACTTA-3', containing a pair of SinR consensus sequences in inverted orientation with a K(d) of 300 nM. The implications of these data for promoter binding and the curious quaternary structural transitions of SinR upon binding to (i) SinI and (ii) the SinR-like protein SlrR, which "repurposes" SinR as a repressor of autolysin and motility genes, are discussed.
GO:0043565
sequence-specific DNA binding
GO:0046983
protein dimerization activity
GO:0006355
regulation of transcription, DNA-templated
GO:0010629
negative regulation of gene expression
GO:0006351
transcription, DNA-templated
GO:0030435
sporulation resulting in formation of a cellular spore
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Other
Other
A
HTH-type transcriptional regulator SinR
Bacillus subtilis
GPAIDSEWEKLVRDAMTSGVSKKQFREFLDYQKWRKSQKEE
41
P06533
71
111
36.9%
UniRef90_P06533
74
111
secondary structure
helix
76
86
secondary structure
helix
94
107
pfam
PF08671.7
SinI
74
101
B
HTH-type transcriptional regulator SinR
Bacillus subtilis
GPAIDSEWEKLVRDAMTSGVSKKQFREFLDYQKWRKSQKEE
41
P06533
71
111
36.9%
UniRef90_P06533
74
111
secondary structure
helix
77
87
secondary structure
helix
92
106
pfam
PF08671.7
SinI
74
101
A
The C-terminal dimerization regions of SirR is highly mobile evading structure determination by X-ray (PMID:23430750).
B
The C-terminal dimerization regions of SirR is highly mobile evading structure determination by X-ray (PMID:23430750).
3zkc
MF2110020
The mid-region of tropomyosin
2b9c
X-ray
2.30
homodimer
Bos taurus
16365313
Brown JH, Zhou Z, Reshetnikova L, Robinson H, Yammani RD, Tobacman LS, Cohen C
Structure of the mid-region of tropomyosin: bending and binding sites for actin.
Proc. Natl. Acad. Sci. U.S.A.
2005
52
102
18878-83
Tropomyosin is a two-chain alpha-helical coiled coil whose periodic interactions with the F-actin helix are critical for thin filament stabilization and the regulation of muscle contraction. Here we deduce the mechanical and chemical basis of these interactions from the 2.3-A-resolution crystal structure of the middle three of tropomyosin's seven periods. Geometrically specific bends of the coiled coil, produced by clusters of core alanines, and variable bends about gaps in the core, produced by isolated alanines, occur along the molecule. The crystal packing is notable in signifying that the functionally important fifth period includes an especially favorable protein-binding site, comprising an unusual apolar patch on the surface together with surrounding charged residues. Based on these and other results, we have constructed a specific model of the thin filament, with the N-terminal halves of each period (i.e., the so-called "alpha zones") of tropomyosin axially aligned with subdomain 3 of each monomer in F-actin.
GO:0003779
actin binding
GO:0005737
cytoplasm
GO:0005856
cytoskeleton
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Coils and zippers
Coiled coil (dimeric)
A
Tropomyosin alpha-1 chain
Bos taurus
MNRRIQLVEEELDRAQERLATALQKLEEAEKAADESERGMKVIESRAQKDEEKMEIQEIQLKEAKHIAEDADRKYEEVARKLVIIESDLERAEERAELSEGKCAELEEELKTVTNNLKSLEDKVEELLSKNYHLENEVARLKKLVGE
147
Q5KR49
88
225
48.6%
UniRef90_P09493
88
225
secondary structure
helix
100
103
secondary structure
helix
108
123
secondary structure
helix
125
209
secondary structure
helix
214
225
pfam
PF00261.17
Tropomyosin
48
284
B
Tropomyosin alpha-1 chain
Bos taurus
MNRRIQLVEEELDRAQERLATALQKLEEAEKAADESERGMKVIESRAQKDEEKMEIQEIQLKEAKHIAEDADRKYEEVARKLVIIESDLERAEERAELSEGKCAELEEELKTVTNNLKSLEDKVEELLSKNYHLENEVARLKKLVGE
147
Q5KR49
88
225
48.6%
UniRef90_P09493
88
225
secondary structure
helix
100
143
secondary structure
helix
145
225
pfam
PF00261.17
Tropomyosin
48
284
The subunits in the structure are bound via coiled coil interactions (PMID:16365313). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
2d3e
2efr
2efs
2tma
MF2120030
Antitoxin RelB
2k29
NMR
homodimer
Escherichia coli
18501926
Li GY, Zhang Y, Inouye M, Ikura M
Structural mechanism of transcriptional autorepression of the Escherichia coli RelB/RelE antitoxin/toxin module.
J. Mol. Biol.
2008
1
380
107-19
The Escherichia coli chromosomal relBE operon encodes a toxin-antitoxin system, which is autoregulated by its protein products, RelB and RelE. RelB acts as a transcriptional repressor and RelE functions as a cofactor to enhance the repressor activity of RelB. Here, we present the NMR-derived structure of a RelB dimer and show that a RelB dimer recognizes a hexad repeat in the palindromic operator region through a ribbon-helix-helix motif. Our biochemical data show that two weakly associated RelB dimers bind to the adjacent repeats in the 3'-site of the operator (O(R)) at a moderate affinity (K(d), approximately 10(-5) M). However, in the presence of RelE, a RelB tetramer binds two distinct binding sites within the operator region, each with an enhanced affinity (K(d), approximately 10(-6) M for the low-affinity site, O(L), and 10(-8) M for the high-affinity site, O(R)). We propose that the enhanced affinity for the operator element is mediated by a cooperative DNA binding by a pair of RelB dimers and that the interaction between RelB dimers is strongly augmented by the presence of the cognate toxin RelE.
GO:0005515
protein binding
GO:0003677
DNA binding
GO:0006355
regulation of transcription, DNA-templated
GO:0006351
transcription, DNA-templated
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Other
Ribbon-helix-helix (RHH)
A
Antitoxin RelB
Escherichia coli
GSHMGSINLRIDDELKARSYAALEKMGVTPSEALRLMLEYIADNERLPFKQTL
53
P0C079
1
50
63.3%
UniRef90_P0C079
1
50
secondary structure
beta
2
8
secondary structure
helix
10
22
secondary structure
helix
27
41
pfam
PF04221.9
RelB
1
79
B
Antitoxin RelB
Escherichia coli
GSHMGSINLRIDDELKARSYAALEKMGVTPSEALRLMLEYIADNERLPFKQTL
53
P0C079
1
50
63.3%
UniRef90_P0C079
1
50
secondary structure
beta
2
8
secondary structure
helix
10
22
secondary structure
helix
27
41
pfam
PF04221.9
RelB
1
79
The interacting chains form a ribbon-helix-helix (RHH) structure (PMID:18501926). These structures in general have been described with the two monomers adopting a stable conformation upon the interaction (PMID:17676053). The hydrophobic core stabilizing the complex is formed by both interactors and is thus absent prior to the interaction (PMID:25713077).
4fxe
MF2140014
Dimerization domain of the rabies virus phosphoprotein
3l32
X-ray
1.50
homodimer
Rabies virus
20089657
Ivanov I, Crépin T, Jamin M, Ruigrok RW
Structure of the dimerization domain of the rabies virus phosphoprotein.
J. Virol.
2010
7
84
3707-10
The crystal structure of the dimerization domain of rabies virus phosphoprotein was determined. The monomer consists of two alpha-helices that make a helical hairpin held together mainly by hydrophobic interactions. The monomer has a hydrophilic and a hydrophobic face, and in the dimer two monomers pack together through their hydrophobic surfaces. This structure is very different from the dimerization domain of the vesicular stomatitis virus phosphoprotein and also from the tetramerization domain of the Sendai virus phosphoprotein, suggesting that oligomerization is conserved but not structure.
GO:0003968
RNA-directed RNA polymerase activity
GO:0039564
suppression by virus of host STAT2 activity
GO:0019083
viral transcription
GO:0046718
viral entry into host cell
GO:0039502
suppression by virus of host type I interferon-mediated signaling pathway
GO:0001172
transcription, RNA-templated
GO:0075521
microtubule-dependent intracellular transport of viral material towards nucleus
GO:0039563
suppression by virus of host STAT1 activity
GO:0042025
host cell nucleus
GO:0019012
virion
GO:0030430
host cell cytoplasm
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Other
Other
A
Phosphoprotein
Rabies virus
MNLLFQSYLDNVGVQIVRQMRSGERFLKIWSQTVEEIVSYVTVNF
45
Q0GBY3
89
133
15.2%
UniRef90_P22363
90
133
secondary structure
helix
91
108
secondary structure
helix
114
132
pfam
PF03012.11
PP_M1
1
296
B
Phosphoprotein
Rabies virus
MNLLFQSYLDNVGVQIVRQMRSGERFLKIWSQTVEEIVSYVTVNF
45
Q0GBY3
89
133
15.2%
UniRef90_P22363
90
133
secondary structure
helix
91
109
secondary structure
helix
114
132
pfam
PF03012.11
PP_M1
1
296
A
The C-terminal dimerization region of SirR is highly mobile evading structure determination by X-ray (PDB:3oa1).
B
The C-terminal dimerization region of SirR is highly mobile evading structure determination by X-ray (PDB:3oa1).
MF2140015
Capsid protein C fragment from dengue virus capsid protein
1r6r
NMR
homodimer
Dengue virus type 2
14993605
Ma L, Jones CT, Groesch TD, Kuhn RJ, Post CB
Solution structure of dengue virus capsid protein reveals another fold.
Proc. Natl. Acad. Sci. U.S.A.
2004
10
101
3414-9
Dengue virus is responsible for approximately 50-100 million infections, resulting in nearly 24,000 deaths annually. The capsid (C) protein of dengue virus is essential for specific encapsidation of the RNA genome, but little structural information on the C protein is available. We report the solution structure of the 200-residue homodimer of dengue 2 C protein. The structure provides, to our knowledge, the first 3D picture of a flavivirus C protein and identifies a fold that includes a large dimerization surface contributed by two pairs of helices, one of which has characteristics of a coiled-coil. NMR structure determination involved a secondary structure sorting approach to facilitate assignment of the intersubunit nuclear Overhauser effect interactions. The dimer of dengue C protein has an unusually high net charge, and the structure reveals an asymmetric distribution of basic residues over the surface of the protein. Nearly half of the basic residues lie along one face of the dimer. In contrast, the conserved hydrophobic region forms an extensive apolar surface at a dimer interface on the opposite side of the molecule. We propose a model for the interaction of dengue C protein with RNA and the viral membrane that is based on the asymmetric charge distribution of the protein and is consistent with previously reported results.
GO:0008026
ATP-dependent helicase activity
GO:0046872
metal ion binding
GO:0003725
double-stranded RNA binding
GO:0004482
mRNA (guanine-N7-)-methyltransferase activity
GO:0003968
RNA-directed RNA polymerase activity
GO:0046983
protein dimerization activity
GO:0070008
serine-type exopeptidase activity
GO:0003724
RNA helicase activity
GO:0004483
mRNA (nucleoside-2'-O-)-methyltransferase activity
GO:0005524
ATP binding
GO:0004252
serine-type endopeptidase activity
GO:0005198
structural molecule activity
GO:0006508
proteolysis
GO:0006351
transcription, DNA-templated
GO:0036265
RNA (guanine-N7)-methylation
GO:0039654
fusion of virus membrane with host endosome membrane
GO:0039502
suppression by virus of host type I interferon-mediated signaling pathway
GO:0006370
7-methylguanosine mRNA capping
GO:0039564
suppression by virus of host STAT2 activity
GO:0001172
transcription, RNA-templated
GO:0039694
viral RNA genome replication
GO:0006355
regulation of transcription, DNA-templated
GO:0075512
clathrin-mediated endocytosis of virus by host cell
GO:0019062
virion attachment to host cell
GO:0080009
mRNA methylation
GO:0039520
induction by virus of host autophagy
GO:0039574
suppression by virus of host TYK2 activity
GO:0019031
viral envelope
GO:0055036
virion membrane
GO:0042025
host cell nucleus
GO:0044167
host cell endoplasmic reticulum membrane
GO:0019028
viral capsid
GO:0005576
extracellular region
GO:0016021
integral component of membrane
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Other
Other
A
Genome polyprotein
Dengue virus type 2
MNDQRKKARNTPFNMLKRERNRVSTVQQLTKRFSLGMLQGRGPLKLFMALVAFLRFLTIPPTAGILKRWGTIKKSKAINVLRGFRKEIGRMLNILNRRRR
100
P12823
1
100
3%
UniRef90_P29991
1
100
secondary structure
helix
27
32
secondary structure
helix
45
57
secondary structure
helix
63
69
secondary structure
helix
75
95
pfam
PF01003.16
Flavi_capsid
5
118
B
Genome polyprotein
Dengue virus type 2
MNDQRKKARNTPFNMLKRERNRVSTVQQLTKRFSLGMLQGRGPLKLFMALVAFLRFLTIPPTAGILKRWGTIKKSKAINVLRGFRKEIGRMLNILNRRRR
100
P12823
1
100
3%
UniRef90_P29991
1
100
secondary structure
helix
27
32
secondary structure
helix
45
57
secondary structure
helix
63
69
secondary structure
helix
75
95
pfam
PF01003.16
Flavi_capsid
5
118
A
The 1-100 region described in DisProt entry DP00876 covers 100% of a close homologue of the sequence present in the structure.
B
The 1-100 region described in DisProt entry DP00876 covers 100% of a close homologue of the sequence present in the structure.
MF2110021
ID2 HLH homodimer
4aya
X-ray
2.10
homodimer
Sus scrofa
23119064
Wong MV, Jiang S, Palasingam P, Kolatkar PR
A Divalent Ion Is Crucial in the Structure and Dominant-Negative Function of ID Proteins, a Class of Helix-Loop-Helix Transcription Regulators.
PLoS ONE
2012
10
7
e48591
Inhibitors of DNA binding and differentiation (ID) proteins, a dominant-negative group of helix-loop-helix (HLH) transcription regulators, are well-characterized key players in cellular fate determination during development in mammals as well as Drosophila. Although not oncogenes themselves, their upregulation by various oncogenic proteins (such as Ras, Myc) and their inhibitory effects on cell cycle proteins (such as pRb) hint at their possible roles in tumorigenesis. Furthermore, their potency as inhibitors of cellular differentiation, through their heterodimerization with subsequent inactivation of the ubiquitous E proteins, suggest possible novel roles in engineering induced pluripotent stem cells (iPSCs). We present the high-resolution 2.1Å crystal structure of ID2 (HLH domain), coupled with novel biochemical insights in the presence of a divalent ion, possibly calcium (Ca2+), in the loop of ID proteins, which appear to be crucial for the structure and activity of ID proteins. These new insights will pave the way for new rational drug designs, in addition to current synthetic peptide options, against this potent player in tumorigenesis as well as more efficient ways for stem cells reprogramming.
GO:0046983
protein dimerization activity
GO:0044325
ion channel binding
GO:0045777
positive regulation of blood pressure
GO:0045648
positive regulation of erythrocyte differentiation
GO:0045893
positive regulation of transcription, DNA-templated
GO:0006351
transcription, DNA-templated
GO:0048541
Peyer's patch development
GO:0021772
olfactory bulb development
GO:0000122
negative regulation of transcription from RNA polymerase II promoter
GO:0014003
oligodendrocyte development
GO:0060612
adipose tissue development
GO:0061031
endodermal digestive tract morphogenesis
GO:0048557
embryonic digestive tract morphogenesis
GO:0048469
cell maturation
GO:0003166
bundle of His development
GO:0032922
circadian regulation of gene expression
GO:0048667
cell morphogenesis involved in neuron differentiation
GO:0045665
negative regulation of neuron differentiation
GO:0045475
locomotor rhythm
GO:2000045
regulation of G1/S transition of mitotic cell cycle
GO:0071285
cellular response to lithium ion
GO:0019216
regulation of lipid metabolic process
GO:0048663
neuron fate commitment
GO:0061030
epithelial cell differentiation involved in mammary gland alveolus development
GO:0090398
cellular senescence
GO:0043153
entrainment of circadian clock by photoperiod
GO:0048715
negative regulation of oligodendrocyte differentiation
GO:0043353
enucleate erythrocyte differentiation
GO:0071158
positive regulation of cell cycle arrest
GO:0048661
positive regulation of smooth muscle cell proliferation
GO:0001966
thigmotaxis
GO:0043392
negative regulation of DNA binding
GO:0045600
positive regulation of fat cell differentiation
GO:2000178
negative regulation of neural precursor cell proliferation
GO:0001656
metanephros development
GO:0033598
mammary gland epithelial cell proliferation
GO:0045668
negative regulation of osteoblast differentiation
GO:0008344
adult locomotory behavior
GO:0045651
positive regulation of macrophage differentiation
GO:0001779
natural killer cell differentiation
GO:0003149
membranous septum morphogenesis
GO:0043433
negative regulation of sequence-specific DNA binding transcription factor activity
GO:0045578
negative regulation of B cell differentiation
GO:0048711
positive regulation of astrocyte differentiation
GO:0005654
nucleoplasm
GO:0005813
centrosome
GO:0005829
cytosol
GO:0043234
protein complex
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Other
Basic helix-loop-helix (bHLH)
A
DNA-binding protein inhibitor ID-2
Sus scrofa
GMKAFSPVRSVRKNSLSDHSLGISRSKTPVDDPMSLLYNMNDCYSKLKELVPSIPQNKKVSKMEILQHVIDYILDLQIALDSHLKPSFLVQSGDIAS
97
Q2VIU1
1
82
61.2%
UniRef90_P41136
1
82
secondary structure
helix
32
49
secondary structure
helix
61
82
pfam
PF00010.23
HLH
35
76
B
DNA-binding protein inhibitor ID-2
Sus scrofa
GMKAFSPVRSVRKNSLSDHSLGISRSKTPVDDPMSLLYNMNDCYSKLKELVPSIPQNKKVSKMEILQHVIDYILDLQIALDSHLKPSFLVQSGDIAS
97
Q2VIU1
1
82
61.2%
UniRef90_P41136
1
82
secondary structure
helix
39
49
secondary structure
helix
61
80
pfam
PF00010.23
HLH
35
76
Monomeric elements of basic helix-loop-helix domains were shown to be natively unfolded with a pH-dependent premolten globule conformation, as shown by several spectroscopic techniques (NMR, fluorescence, FTIR, and circular dichroism) (PMID:20102160, PMID:8303294).
MF2110022
Cobra venom nerve growth factor (NGF)
4ec7
X-ray
2.60
homodimer
Naja atra
22649032
Tong Q, Wang F, Zhou HZ, Sun HL, Song H, Shu YY, Gong Y, Zhang WT, Cai TX, Yang FQ, Tang J, Jiang T
Structural and functional insights into lipid-bound nerve growth factors.
FASEB J.
2012
9
26
3811-21
Nerve growth factor (NGF) is a dimeric molecule that modulates the survival, proliferation, and differentiation of nervous cells and is also known to act on cells of the immune system and endocrine system. NGFs extracted from mouse submaxillary gland and cobra venom have different immunological behaviors, yet the underlying mechanism remains unclear. Here we report the crystal structure of the NGF purified from Chinese cobra Naja naja atra (cNGF), which unexpectedly reveals a 2-tailed lipid molecule that is embedded between the two protomers of the NGF homodimer. In addition, crystallographic analysis indicated that the purified mouse NGF(mNGF) is free from lipid but can bind lysophosphatidylserine (lyso-PS) in the same pocket as cNGF. Bioassays indicated that the binding of lipid molecules to cNGF and mNGF are essential for their mast cell activation activity and abates their p75(NTR) binding capacity. Taken together, these results suggest a new mechanism for the regulation of the function of NGF.-Tong, Q., Wang, F., Zhou, H.-Z., Sun, H.-L., Song, H., Shu, Y.-Y., Gong, Y., Zhang, W.-T., Cai, T.-X., Yang, F.-Q., Tang, J., Jiang, T. Structural and functional insights into lipid-bound nerve growth factors.
GO:0008083
growth factor activity
GO:0008191
metalloendopeptidase inhibitor activity
GO:0010951
negative regulation of endopeptidase activity
GO:0005576
extracellular region
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
NGF-like proteins
Homodimeric NGF-like proteins
A
Venom nerve growth factor
Naja atra
EDHPVHNLGEHSVCDSVSAWVTKTTATDIKGNTVTVMENVNLDNKVYKEYFFETKCKNPNPEPSGCRGIDSSHWNSYCTETDTFIKALTMEGNQASWRFIRIETACVCVITKKKGN
116
P61898
1
116
100%
UniRef90_P61898
1
116
secondary structure
beta
11
12
secondary structure
beta
16
21
secondary structure
beta
25
28
secondary structure
beta
33
36
secondary structure
beta
39
42
secondary structure
beta
45
48
secondary structure
beta
51
56
secondary structure
beta
62
62
secondary structure
beta
65
65
secondary structure
beta
69
69
secondary structure
beta
74
91
secondary structure
beta
94
112
pfam
PF00243.15
NGF
6
115
B
Venom nerve growth factor
Naja atra
EDHPVHNLGEHSVCDSVSAWVTKTTATDIKGNTVTVMENVNLDNKVYKEYFFETKCKNPNPEPSGCRGIDSSHWNSYCTETDTFIKALTMEGNQASWRFIRIETACVCVITKKKGN
116
P61898
1
116
100%
UniRef90_P61898
1
116
secondary structure
beta
11
12
secondary structure
beta
16
21
secondary structure
beta
25
28
secondary structure
beta
33
36
secondary structure
beta
39
41
secondary structure
beta
46
48
secondary structure
beta
51
56
secondary structure
beta
62
62
secondary structure
beta
65
65
secondary structure
beta
69
69
secondary structure
beta
76
91
secondary structure
beta
94
110
pfam
PF00243.15
NGF
6
115
Various dimeric members of neurotrophic factors (including human/mouse nerve growth factor, human brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4/5 (NT-4/5)) have been shown to fold and dimerize at the same time via a two-state process (PMID:8161524). While the members of this family show a significant variance in sequence, they adopt a highly similar structure upon binding and behave almost identically in unfolding/refolding experiments. Thus the two-state folding/binding nature seems to be a hallmark of NGF and closely related proteins.
MF2120031
SopB dimerization domain
3kz5
X-ray
1.58
homodimer
Escherichia coli
20236989
Schumacher MA, Piro KM, Xu W
Insight into F plasmid DNA segregation revealed by structures of SopB and SopB-DNA complexes.
Nucleic Acids Res.
2010
13
38
4514-26
Accurate DNA segregation is essential for genome transmission. Segregation of the prototypical F plasmid requires the centromere-binding protein SopB, the NTPase SopA and the sopC centromere. SopB displays an intriguing range of DNA-binding properties essential for partition; it binds sopC to form a partition complex, which recruits SopA, and it also coats DNA to prevent non-specific SopA-DNA interactions, which inhibits SopA polymerization. To understand the myriad functions of SopB, we determined a series of SopB-DNA crystal structures. SopB does not distort its DNA site and our data suggest that SopB-sopC forms an extended rather than wrapped partition complex with the SopA-interacting domains aligned on one face. SopB is a multidomain protein, which like P1 ParB contains an all-helical DNA-binding domain that is flexibly attached to a compact (beta(3)-alpha)(2) dimer-domain. Unlike P1 ParB, the SopB dimer-domain does not bind DNA. Moreover, SopB contains a unique secondary dimerization motif that bridges between DNA duplexes. Both specific and non-specific SopB-DNA bridging structures were observed. This DNA-linking function suggests a novel mechanism for in trans DNA spreading by SopB, explaining how it might mask DNA to prevent DNA-mediated inhibition of SopA polymerization.
GO:0003677
DNA binding
GO:0030541
plasmid partitioning
Chain A was removed as chains B and E represent the biologically relevant dimer.
2
1
Other
Other
B
Protein SopB
Escherichia coli
GSHMSSRHQFAPGATVLYKGDKMVLNLDRSRVPTECIEKIEAILKELEKPAP
52
P62558
272
323
16.1%
UniRef90_P62559
279
323
secondary structure
beta
279
282
secondary structure
beta
285
290
secondary structure
beta
293
299
secondary structure
helix
305
318
E
Protein SopB
Escherichia coli
GSHMSSRHQFAPGATVLYKGDKMVLNLDRSRVPTECIEKIEAILKELEKPAP
52
P62558
272
323
16.1%
UniRef90_P62559
279
323
secondary structure
beta
279
282
secondary structure
beta
285
290
secondary structure
beta
293
299
secondary structure
helix
305
318
B
The C-terminal dimerization region of SopB is highly mobile evading structure determination by X-ray (PMID:20236989).
E
The C-terminal dimerization region of SopB is highly mobile evading structure determination by X-ray (PMID:20236989).
MF2110023
Basic HLH/leucine zipper domain of apo MITF
4ath
X-ray
1.95
homodimer
Mus musculus
23207919
Pogenberg V, Ogmundsdóttir MH, Bergsteinsdóttir K, Schepsky A, Phung B, Deineko V, Milewski M, Steingrímsson E, Wilmanns M
Restricted leucine zipper dimerization and specificity of DNA recognition of the melanocyte master regulator MITF.
Genes Dev.
2012
23
26
2647-58
Microphthalmia-associated transcription factor (MITF) is a master regulator of melanocyte development and an important oncogene in melanoma. MITF heterodimeric assembly with related basic helix-loop-helix leucine zipper transcription factors is highly restricted, and its binding profile to cognate DNA sequences is distinct. Here, we determined the crystal structure of MITF in its apo conformation and in the presence of two related DNA response elements, the E-box and M-box. In addition, we investigated mouse and human Mitf mutations to dissect the functional significance of structural features. Owing to an unusual three-residue shift in the leucine zipper register, the MITF homodimer shows a marked kink in one of the two zipper helices to allow an out-of-register assembly. Removal of this insertion relieves restricted heterodimerization by MITF and permits assembly with the transcription factor MAX. Binding of MITF to the M-box motif is mediated by an unusual nonpolar interaction by Ile212, a residue that is mutated in mice and humans with Waardenburg syndrome. As several related transcription factors have low affinity for the M-box sequence, our analysis unravels how these proteins discriminate between similar target sequences. Our data provide a rational basis for targeting MITF in the treatment of important hereditary diseases and cancer.
GO:0046983
protein dimerization activity
GO:0003682
chromatin binding
GO:0000978
RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0003705
transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding
GO:0000979
RNA polymerase II core promoter sequence-specific DNA binding
GO:0001077
transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0030318
melanocyte differentiation
GO:0006461
protein complex assembly
GO:0044336
canonical Wnt signaling pathway involved in negative regulation of apoptotic process
GO:0046849
bone remodeling
GO:0045944
positive regulation of transcription from RNA polymerase II promoter
GO:0006366
transcription from RNA polymerase II promoter
GO:2000144
positive regulation of DNA-templated transcription, initiation
GO:0000122
negative regulation of transcription from RNA polymerase II promoter
GO:0045165
cell fate commitment
GO:0045670
regulation of osteoclast differentiation
GO:0097531
mast cell migration
GO:0030316
osteoclast differentiation
GO:0043010
camera-type eye development
GO:0042127
regulation of cell proliferation
GO:0005634
nucleus
GO:0043234
protein complex
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Other
Basic helix-loop-helix (bHLH)
A
Microphthalmia-associated transcription factor
Mus musculus
GAMRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKDLENRQKKLEHANRHLLLRVQELEMQARAHG
83
Q08874
321
403
15.8%
UniRef90_O75030
324
403
secondary structure
helix
325
338
secondary structure
helix
352
368
secondary structure
helix
370
396
secondary structure
helix
398
402
pfam
PF00010.23
HLH
312
365
B
Microphthalmia-associated transcription factor
Mus musculus
GAMRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKDLENRQKKLEHANRHLLLRVQELEMQARAHG
83
Q08874
321
403
15.8%
UniRef90_O75030
324
403
secondary structure
helix
324
338
secondary structure
helix
352
396
secondary structure
helix
398
402
pfam
PF00010.23
HLH
312
365
Monomeric elements of basic helix-loop-helix domains were shown to be natively unfolded with a pH-dependent premolten globule conformation, as shown by several spectroscopic techniques (NMR, fluorescence, FTIR, and circular dichroism) (PMID:20102160, PMID:8303294).
4ati
4atk
MF3100003
Vimentin coil 1B fragment (trimeric)
4ypc
X-ray
1.44
homotrimer
Homo sapiens
26795465
Chernyatina AA, Hess JF, Guzenko D, Voss JC, Strelkov SV
How to Study Intermediate Filaments in Atomic Detail.
Meth. Enzymol.
2016
568
3-33
Studies of the intermediate filament (IF) structure are a prerequisite of understanding their function. In addition, the structural information is indispensable if one wishes to gain a mechanistic view on the disease-related mutations in the IFs. Over the years, considerable progress has been made on the atomic structure of the elementary building block of all IFs, the coiled-coil dimer. Here, we discuss the approaches, methods and practices that have contributed to this advance. With abundant genetic information on hand, bioinformatics approaches give important insights into the dimer structure, including the head and tail regions poorly assessable experimentally. At the same time, the most important contribution has been provided by X-ray crystallography. Following the "divide-and-conquer" approach, many fragments from several IF proteins could be crystallized and resolved to atomic resolution. We will systematically cover the main procedures of these crystallographic studies, suggest ways to maximize their efficiency, and also discuss the possible pitfalls and limitations. In addition, electron paramagnetic resonance with site-directed spin labeling was another method providing a major impact toward the understanding of the IF structure. Upon placing the spin labels into specific positions within the full-length protein, one can evaluate the proximity of the labels and their mobility. This makes it possible to make conclusions about the dimer structure in the coiled-coil region and beyond, as well as to explore the dimer-dimer contacts.
GO:0008022
protein C-terminus binding
GO:0005212
structural constituent of eye lens
GO:0042802
identical protein binding
GO:0097110
scaffold protein binding
GO:0005200
structural constituent of cytoskeleton
GO:1990254
keratin filament binding
GO:0003725
double-stranded RNA binding
GO:0001948
glycoprotein binding
GO:0060020
Bergmann glial cell differentiation
GO:0010977
negative regulation of neuron projection development
GO:0070307
lens fiber cell development
GO:0030049
muscle filament sliding
GO:0045109
intermediate filament organization
GO:0060395
SMAD protein signal transduction
GO:0010628
positive regulation of gene expression
GO:0016032
viral process
GO:0014002
astrocyte development
GO:0070062
extracellular exosome
GO:0005882
intermediate filament
GO:0031012
extracellular matrix
GO:0005829
cytosol
GO:0031252
cell leading edge
GO:0005886
plasma membrane
GO:0005777
peroxisome
GO:0043005
neuron projection
GO:0005925
focal adhesion
Chains B and C were generated from chain A using the biomatrices described in the original PDB file.
3
1
Coils and zippers
Coiled coil (trimeric)
A
Vimentin
Homo sapiens
VDQLTNDKARVEVERDNLAEDIMRLREKLQEEMLQREEAENTLQSFRQDVDNASLARLDLERKVESLQEEIAFLKKLHEEEIQ
83
P08670
161
243
17.8%
UniRef90_P08670
161
243
secondary structure
helix
167
235
pfam
PF00038.18
Filament
102
410
B
Vimentin
Homo sapiens
VDQLTNDKARVEVERDNLAEDIMRLREKLQEEMLQREEAENTLQSFRQDVDNASLARLDLERKVESLQEEIAFLKKLHEEEIQ
83
P08670
161
243
17.8%
UniRef90_P08670
161
243
secondary structure
helix
167
235
pfam
PF00038.18
Filament
102
410
C
Vimentin
Homo sapiens
VDQLTNDKARVEVERDNLAEDIMRLREKLQEEMLQREEAENTLQSFRQDVDNASLARLDLERKVESLQEEIAFLKKLHEEEIQ
83
P08670
161
243
17.8%
UniRef90_P08670
161
243
secondary structure
helix
167
235
pfam
PF00038.18
Filament
102
410
The subunits in the structure are bound via coiled coil interactions (PMID:26795465). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
4yv3
MF2130002
Methionyl-tRNA synthetase from Pyrococcus abyssi
1mkh
X-ray
2.01
homodimer
Pyrococcus abyssi
12390027
Crepin T, Schmitt E, Blanquet S, Mechulam Y
Structure and function of the C-terminal domain of methionyl-tRNA synthetase.
Biochemistry
2002
43
41
13003-11
The minimal polypeptide supporting full methionyl-tRNA synthetase (MetRS) activity is composed of four domains: a catalytic Rossmann fold, a connective peptide, a KMSKS domain, and a C-terminal alpha helix bundle domain. The minimal MetRS behaves as a monomer. In several species, MetRS is a homodimer because of a C-terminal domain appended to the core polypeptide. Upon truncation of this C-terminal domain, subunits dissociate irreversibly. Here, the C-terminal domain of dimeric MetRS from Pyrococcus abyssi was isolated and studied. It displays nonspecific tRNA-binding properties and has a crystalline structure closely resembling that of Trbp111, a dimeric tRNA-binding protein found in many bacteria and archaea. The obtained 3D model was used to direct mutations against dimerization of Escherichia coli MetRS. Comparison of the resulting mutants to native and C-truncated MetRS shows that the presence of the appended C-domain improves tRNA(Met) binding affinity. However, dimer formation is required to evidence the gain in affinity.
GO:0000049
tRNA binding
GO:0004825
methionine-tRNA ligase activity
GO:0005524
ATP binding
GO:0046872
metal ion binding
GO:0006431
methionyl-tRNA aminoacylation
GO:0005737
cytoplasm
Chain B was generated from chain A using the biomatrix described in the original PDB file.
2
1
Other
Other
A
Methionine--tRNA ligase
Pyrococcus abyssi
MYVKFDDFAKLDLRVGKIIEVKDHPNADKLYVVKVDLGDEVRTLVAGLKKYYKPEELLNRYVVVVANLEPKKLRGIGSQGMLLAADDGERVALLMPDKEVKLGAKVR
107
Q9V011
616
722
14.8%
UniRef90_Q9V011
616
722
secondary structure
beta
618
618
secondary structure
helix
620
624
secondary structure
beta
628
638
secondary structure
beta
646
651
secondary structure
beta
656
661
secondary structure
helix
669
672
secondary structure
beta
676
680
secondary structure
beta
683
683
secondary structure
beta
686
687
secondary structure
beta
692
693
secondary structure
beta
697
697
secondary structure
beta
699
701
secondary structure
beta
706
711
secondary structure
beta
720
721
pfam
PF01588.17
tRNA_bind
628
720
B
Methionine--tRNA ligase
Pyrococcus abyssi
MYVKFDDFAKLDLRVGKIIEVKDHPNADKLYVVKVDLGDEVRTLVAGLKKYYKPEELLNRYVVVVANLEPKKLRGIGSQGMLLAADDGERVALLMPDKEVKLGAKVR
107
Q9V011
616
722
14.8%
UniRef90_Q9V011
616
722
secondary structure
beta
618
618
secondary structure
helix
620
624
secondary structure
beta
628
638
secondary structure
beta
646
651
secondary structure
beta
656
661
secondary structure
helix
669
672
secondary structure
beta
676
680
secondary structure
beta
683
683
secondary structure
beta
686
687
secondary structure
beta
692
693
secondary structure
beta
697
697
secondary structure
beta
699
701
secondary structure
beta
706
711
secondary structure
beta
720
721
pfam
PF01588.17
tRNA_bind
628
720
A
The C-terminal dimerization region of methionyl-tRNA synthetase is highly mobile evading structure determination by X-ray (PMID:14992601).
B
The C-terminal dimerization region of methionyl-tRNA synthetase is highly mobile evading structure determination by X-ray (PMID:14992601).
MF2220002
PE25-PPE41 heterodimer from M. tuberculosis
4w4k
X-ray
1.95
heterodimer
Mycobacterium tuberculosis
25275011
Ekiert DC, Cox JS
Structure of a PE-PPE-EspG complex from Mycobacterium tuberculosis reveals molecular specificity of ESX protein secretion.
Proc. Natl. Acad. Sci. U.S.A.
2014
Nearly 10% of the coding capacity of the Mycobacterium tuberculosis genome is devoted to two highly expanded and enigmatic protein families called PE and PPE, some of which are important virulence/immunogenicity factors and are secreted during infection via a unique alternative secretory system termed "type VII." How PE-PPE proteins function during infection and how they are translocated to the bacterial surface through the five distinct type VII secretion systems [ESAT-6 secretion system (ESX)] of M. tuberculosis is poorly understood. Here, we report the crystal structure of a PE-PPE heterodimer bound to ESX secretion-associated protein G (EspG), which adopts a novel fold. This PE-PPE-EspG complex, along with structures of two additional EspGs, suggests that EspG acts as an adaptor that recognizes specific PE-PPE protein complexes via extensive interactions with PPE domains, and delivers them to ESX machinery for secretion. Surprisingly, secretion of most PE-PPE proteins in M. tuberculosis is likely mediated by EspG from the ESX-5 system, underscoring the importance of ESX-5 in mycobacterial pathogenesis. Moreover, our results indicate that PE-PPE domains function as cis-acting targeting sequences that are read out by EspGs, revealing the molecular specificity for secretion through distinct ESX pathways.
Chains C and D were removed as chains A and B represent the biologically relevant dimer.
2
2
Other
Other
A
PE family protein
Mycobacterium tuberculosis
MHHHHHHENLYFQTNPEALTVAATEVRRIRDRAIQSDAQVAPMTTAVRPPAADLVSEKAATFLVEYARKYRQTIAAAAVVLEEFAHALTTGADKYATAEADNIKTFS
107
A0A0H3LBR3
5
98
94.9%
UniRef90_UPI0005092AC7
1
107
secondary structure
helix
9
36
secondary structure
helix
46
86
pfam
PF00934.17
PE
1
93
B
PPE family protein
Mycobacterium tuberculosis
MHFEAYPPEVNSANIYAGPGPDSMLAAARAWRSLDVEMTAVQRSFNRTLLSLMDAWAGPVVMQLMEAAKPFVRWLTDLCVQLSEVERQIHEIVRAYEWAHHDMVPLAQIYNNRAERQILIDNNALGQFTAQIADLDQEYDDFWDEDGEVMRDYRLRVSDALSKLTPWKAPPPIA
174
A0A0H3LBN6
1
174
89.7%
UniRef90_Q79FE1
1
174
secondary structure
helix
3
5
secondary structure
helix
8
17
secondary structure
helix
22
53
secondary structure
helix
59
67
secondary structure
helix
69
102
secondary structure
helix
106
121
secondary structure
helix
129
161
pfam
PF00823.16
PPE
5
161
Both proteins involved in the interaction evade successful expression, purification and crystallization in their monomeric form, owing to the fact that both proteins are disordered and are extremely susceptible to degradation (PMID:16690741).
2g38
4w4l
4kxr
MF2100015
Vimentin coil 1B fragment (dimeric)
3ssu
X-ray
2.60
homodimer
Homo sapiens
22869704
Chernyatina AA, Nicolet S, Aebi U, Herrmann H, Strelkov SV
Atomic structure of the vimentin central α-helical domain and its implications for intermediate filament assembly.
Proc. Natl. Acad. Sci. U.S.A.
2012
34
109
13620-5
Together with actin filaments and microtubules, intermediate filaments (IFs) are the basic cytoskeletal components of metazoan cells. Over 80 human diseases have been linked to mutations in various IF proteins to date. However, the filament structure is far from being resolved at the atomic level, which hampers rational understanding of IF pathologies. The elementary building block of all IF proteins is a dimer consisting of an α-helical coiled-coil (CC) "rod" domain flanked by the flexible head and tail domains. Here we present three crystal structures of overlapping human vimentin fragments that comprise the first half of its rod domain. Given the previously solved fragments, a nearly complete atomic structure of the vimentin rod has become available. It consists of three α-helical segments (coils 1A, 1B, and 2) interconnected by linkers (L1 and L12). Most of the CC structure has a left-handed twist with heptad repeats, but both coil 1B and coil 2 also exhibit untwisted, parallel stretches with hendecad repeats. In the crystal structure, linker L1 was found to be α-helical without being involved in the CC formation. The available data allow us to construct an atomic model of the antiparallel tetramer representing the second level of vimentin assembly. Although the presence of the nonhelical head domains is essential for proper tetramer stabilization, the precise alignment of the dimers forming the tetramer appears to depend on the complementarity of their surface charge distribution patterns, while the structural plasticity of linker L1 and coil 1A plays a role in the subsequent IF assembly process.
GO:0008022
protein C-terminus binding
GO:0005212
structural constituent of eye lens
GO:0042802
identical protein binding
GO:0097110
scaffold protein binding
GO:0005200
structural constituent of cytoskeleton
GO:1990254
keratin filament binding
GO:0003725
double-stranded RNA binding
GO:0001948
glycoprotein binding
GO:0060020
Bergmann glial cell differentiation
GO:0010977
negative regulation of neuron projection development
GO:0070307
lens fiber cell development
GO:0030049
muscle filament sliding
GO:0045109
intermediate filament organization
GO:0060395
SMAD protein signal transduction
GO:0010628
positive regulation of gene expression
GO:0016032
viral process
GO:0014002
astrocyte development
GO:0070062
extracellular exosome
GO:0005882
intermediate filament
GO:0031012
extracellular matrix
GO:0005829
cytosol
GO:0031252
cell leading edge
GO:0005886
plasma membrane
GO:0005777
peroxisome
GO:0043005
neuron projection
GO:0005925
focal adhesion
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Coils and zippers
Coiled coil (dimeric)
A
Vimentin
Homo sapiens
GSTRTNEKVELQELNDRFANYIDKVRFLEQQNKILLAELEQLKGQGKSRLGDLYEEEMRELRRQVDQLTNDKARVEVERDNLAEDIMRLREKL
93
P08670
97
189
20%
UniRef90_P08670
99
189
secondary structure
helix
145
187
pfam
PF00038.18
Filament
102
410
B
Vimentin
Homo sapiens
GSTRTNEKVELQELNDRFANYIDKVRFLEQQNKILLAELEQLKGQGKSRLGDLYEEEMRELRRQVDQLTNDKARVEVERDNLAEDIMRLREKL
93
P08670
97
189
20%
UniRef90_P08670
99
189
secondary structure
helix
150
186
pfam
PF00038.18
Filament
102
410
The subunits in the structure are bound via coiled coil interactions (PMID:22869704). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
3s4r
3g1e
3swk
3uf1
MF2100016
TRIM25 coiled-coil
4cfg
X-ray
2.80
homodimer
Homo sapiens
James, L.
Structure of the Trim25 Coiled-Coil
To be published
-
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Coils and zippers
Coiled coil (dimeric)
A
E3 ubiquitin/ISG15 ligase TRIM25
Homo sapiens
MAELCPLAEELSCSICLEPFKEPVTTPCGHNFCGSCLNETWAVQGSPYLCPQCRAVYQARPQLHKNTVLCNVVEQFLQADLAREPPADVWTPPARASAPSPNAQVACDHCLKEAAVKTCLVCMASFCQEHLQPHFDSPAFQDHPLQPPVRDLLRRKCSQHNRLREFFCPEHSECICHICLVEHKTCSPASLSQASADLEATLRHKLTVMYSQINGASRALDDVRNRQQDVRMTANRKVEQLQQEYTEMKALLDASETTSTRKIKEEEKRVNSQFDTIYQILLKKKSEIQTLKEEIEQSLTKRDEFEFLEKASKLRGISTQPVYIPEVELNHKLIKGIHQSTIDLKNELKQCIGRLQEPTPSSGDPGEHDPASTHKSTRPVKKVSKEEKKSKKPPPVPALPSKLPTFGAPEQLVDLKQAGLEAAAKATSSHPNSTSLKAKVLETFLAKSRPELLEYYIKVILDYNTAHNKVALSECYTVASVAEMPQNYRPHPQRFTYCSQVLGLHCYKKGIHYWEVELQKNNFCGVGICYGSMNRQGPESRLGRNSASWCVEWFNTKISAWHNNVEKTLPSTKATRVGVLLNCDHGFVIFFAVADKVHLMYKFRVDFTEALYPAFWVFSAGATLSICSPK
630
Q14258
194
357
26%
UniRef90_Q14258
194
357
secondary structure
helix
195
208
secondary structure
helix
210
231
secondary structure
helix
233
247
secondary structure
helix
249
304
secondary structure
helix
307
317
secondary structure
helix
334
357
B
E3 ubiquitin/ISG15 ligase TRIM25
Homo sapiens
MAELCPLAEELSCSICLEPFKEPVTTPCGHNFCGSCLNETWAVQGSPYLCPQCRAVYQARPQLHKNTVLCNVVEQFLQADLAREPPADVWTPPARASAPSPNAQVACDHCLKEAAVKTCLVCMASFCQEHLQPHFDSPAFQDHPLQPPVRDLLRRKCSQHNRLREFFCPEHSECICHICLVEHKTCSPASLSQASADLEATLRHKLTVMYSQINGASRALDDVRNRQQDVRMTANRKVEQLQQEYTEMKALLDASETTSTRKIKEEEKRVNSQFDTIYQILLKKKSEIQTLKEEIEQSLTKRDEFEFLEKASKLRGISTQPVYIPEVELNHKLIKGIHQSTIDLKNELKQCIGRLQEPTPSSGDPGEHDPASTHKSTRPVKKVSKEEKKSKKPPPVPALPSKLPTFGAPEQLVDLKQAGLEAAAKATSSHPNSTSLKAKVLETFLAKSRPELLEYYIKVILDYNTAHNKVALSECYTVASVAEMPQNYRPHPQRFTYCSQVLGLHCYKKGIHYWEVELQKNNFCGVGICYGSMNRQGPESRLGRNSASWCVEWFNTKISAWHNNVEKTLPSTKATRVGVLLNCDHGFVIFFAVADKVHLMYKFRVDFTEALYPAFWVFSAGATLSICSPK
630
Q14258
194
357
26%
UniRef90_Q14258
194
357
secondary structure
helix
197
208
secondary structure
helix
210
231
secondary structure
helix
233
247
secondary structure
helix
249
303
secondary structure
helix
308
318
secondary structure
helix
334
356
The subunits in the structure are bound via coiled coil interactions (PMID:24550273). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
4ltb
MF4200001
OPTN:TBK1 complex
5eof
X-ray
2.05
heterotetramer
Homo sapiens
27620379
Li F, Xie X, Wang Y, Liu J, Cheng X, Guo Y, Gong Y, Hu S, Pan L
Structural insights into the interaction and disease mechanism of neurodegenerative disease-associated optineurin and TBK1 proteins.
Nat Commun
2016
7
12708
Optineurin is an important autophagy receptor involved in several selective autophagy processes, during which its function is regulated by TBK1. Mutations of optineurin and TBK1 are both associated with neurodegenerative diseases. However, the mechanistic basis underlying the specific interaction between optineurin and TBK1 is still elusive. Here we determine the crystal structures of optineurin/TBK1 complex and the related NAP1/TBK1 complex, uncovering the detailed molecular mechanism governing the optineurin and TBK1 interaction, and revealing a general binding mode between TBK1 and its associated adaptor proteins. In addition, we demonstrate that the glaucoma-associated optineurin E50K mutation not only enhances the interaction between optineurin and TBK1 but also alters the oligomeric state of optineurin, and the ALS-related TBK1 E696K mutation specifically disrupts the optineurin/TBK1 complex formation but has little effect on the NAP1/TBK1 complex. Thus, our study provides mechanistic insights into those currently known disease-causing optineurin and TBK1 mutations found in patients.
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
2
Coils and zippers
Coiled coil (tetrameric)
A
Optineurin
Homo sapiens
GPGSHLAHPNLDTFTPEELLQQMKELLTENHQLKEAMKLNNQAMKGRFEELSAWTEKQKEERQFFEIQSKEAKERLMALSHE
82
Q96CV9
26
103
13.5%
UniRef90_Q96CV9
26
103
secondary structure
helix
37
98
pfam
PF11577.5
NEMO
37
104
B
Optineurin
Homo sapiens
GPGSHLAHPNLDTFTPEELLQQMKELLTENHQLKEAMKLNNQAMKGRFEELSAWTEKQKEERQFFEIQSKEAKERLMALSHE
82
Q96CV9
26
103
13.5%
UniRef90_Q96CV9
26
103
secondary structure
helix
37
101
pfam
PF11577.5
NEMO
37
104
C
Serine/threonine-protein kinase TBK1
Homo sapiens
GPGSYPSSNTLVEMTLGMKKLKEEMEGVVKELAENNHILERFGSLTMDGGLRNVDCL
57
Q9UHD2
677
729
7.3%
UniRef90_Q9UHD2
677
729
secondary structure
helix
680
714
D
Serine/threonine-protein kinase TBK1
Homo sapiens
GPGSYPSSNTLVEMTLGMKKLKEEMEGVVKELAENNHILERFGSLTMDGGLRNVDCL
57
Q9UHD2
677
729
7.3%
UniRef90_Q9UHD2
677
729
secondary structure
helix
680
718
The subunits in the structure are bound via coiled coil interactions (PMID:27620379). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
5eoa
MF4200002
p63/p73 hetero-tetramerization domain (human)
2nb1
NMR
heterotetramer (dimer of dimers)
Homo sapiens
27716744
Gebel J, Luh LM, Coutandin D, Osterburg C, Löhr F, Schäfer B, Frombach AS, Sumyk M, Buchner L, Krojer T, Salah E, Mathea S, Güntert P, Knapp S, Dötsch V
Mechanism of TAp73 inhibition by ΔNp63 and structural basis of p63/p73 hetero-tetramerization.
Cell Death Differ.
2016
Members of the p53 tumor-suppressor family are expressed as multiple isoforms. Isoforms with an N-terminal transactivation domain are transcriptionally active, while those ones lacking this domain often inhibit the transcriptional activity of other family members. In squamous cell carcinomas, the high expression level of ΔNp63α inhibits the tumor-suppressor function of TAp73β. This can in principle be due to blocking of the promoter or by direct interaction between both proteins. p63 and p73 can hetero-oligomerize through their tetramerization domains and a hetero-tetramer consisting of two p63 and two p73 molecules is thermodynamically more stable than both homo-tetramers. Here we show that cells expressing both p63 and p73 exist in mouse epidermis and hair follicle and that hetero-tetramer complexes can be detected by immunoprecipitation in differentiating keratinocytes. Through structure determination of the hetero-tetramer, we reveal why this hetero-tetramer is the thermodynamically preferred species. We have created mutants that exclusively form either hetero-tetramers or homo-tetramers, allowing to investigate the function of these p63/p73 hetero-tetramers. Using these tools, we show that inhibition of TAp73β in squamous cell carcinomas is due to promoter squelching and not direct interaction.Cell Death and Differentiation advance online publication, 7 October 2016; doi:10.1038/cdd.2016.83.
GO:0043565
sequence-specific DNA binding
GO:0003684
damaged DNA binding
GO:0001077
transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0002039
p53 binding
GO:0042802
identical protein binding
GO:0003682
chromatin binding
GO:0046872
metal ion binding
GO:0044212
transcription regulatory region DNA binding
GO:1901796
regulation of signal transduction by p53 class mediator
GO:0006978
DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator
GO:1900740
positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
GO:0042771
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:0010332
response to gamma radiation
GO:0010165
response to X-ray
GO:0034644
cellular response to UV
GO:0051262
protein tetramerization
GO:0031571
mitotic G1 DNA damage checkpoint
GO:0006366
transcription from RNA polymerase II promoter
GO:0045944
positive regulation of transcription from RNA polymerase II promoter
GO:0000122
negative regulation of transcription from RNA polymerase II promoter
GO:0005739
mitochondrion
GO:0005667
transcription factor complex
GO:0005829
cytosol
GO:0005654
nucleoplasm
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
2
Other
p53 tetramerization
A
Tumor protein 63
Homo sapiens
SDDELLYLPVRGRETYEMLLEIKESLELMQYLPQHTIETYRQQQQQQHQHLLQKQTSIQS
60
Q9H3D4
397
455
8.7%
UniRef90_Q9H3D4
397
455
secondary structure
beta
401
401
secondary structure
beta
404
405
secondary structure
helix
408
426
secondary structure
helix
430
445
pfam
PF07710.8
P53_tetramer
391
431
B
Tumor protein p73
Homo sapiens
GSDEDTYYLQVRGRKNFEILMKLKESLELMELVPQPLVDSYRQQQQLLQR
50
O15350
351
398
7.5%
UniRef90_O15350
351
398
secondary structure
beta
355
359
secondary structure
helix
362
380
secondary structure
helix
384
389
pfam
PF07710.8
P53_tetramer
345
384
C
Tumor protein 63
Homo sapiens
SDDELLYLPVRGRETYEMLLEIKESLELMQYLPQHTIETYRQQQQQQHQHLLQKQTSIQS
60
Q9H3D4
397
455
8.7%
UniRef90_Q9H3D4
397
455
secondary structure
beta
401
402
secondary structure
beta
405
405
secondary structure
helix
408
426
secondary structure
helix
430
445
pfam
PF07710.8
P53_tetramer
391
431
D
Tumor protein p73
Homo sapiens
GSDEDTYYLQVRGRKNFEILMKLKESLELMELVPQPLVDSYRQQQQLLQR
50
O15350
351
398
7.5%
UniRef90_O15350
351
398
secondary structure
beta
355
359
secondary structure
helix
362
380
secondary structure
helix
384
389
pfam
PF07710.8
P53_tetramer
345
384
p63 and p73 are members of the p53 protein family. The tetramerization region of p53, p63 and p73 are closely homologous to each other, having very similar sequences, structures and biological functions (PMID:25185827, PMID:18289041, PMID:20379196), all containing the same Pfam domain (PF07710). The tetramerization domain of p53 exhibits a four-helix bundle structure bound by hydrophobic and electrostatic interactions (PMID:8023159). The tetramer is formed as a dimer of dimers and follows a two state folding and binding process, demonstrated in several chemical and thermal denaturation/refolding experiments (PMID:9582268, PMID:18410249, PMID:19913028).
MF2200012
Leukemia Fusion Target AF9 in complex with AF4
2lm0
NMR
heterodimer
Homo sapiens
23260655
Leach BI, Kuntimaddi A, Schmidt CR, Cierpicki T, Johnson SA, Bushweller JH
Leukemia Fusion Target AF9 Is an Intrinsically Disordered Transcriptional Regulator that Recruits Multiple Partners via Coupled Folding and Binding.
Structure
2012
Mixed lineage leukemia (MLL) fusion proteins cause oncogenic transformation of hematopoietic cells by constitutive recruitment of elongation factors to HOX promoters, resulting in overexpression of target genes. The structural basis of transactivation by MLL fusion partners remains undetermined. We show that the ANC1 homology domain (AHD) of AF9, one of the most common MLL translocation partners, is intrinsically disordered and recruits multiple transcription factors through coupled folding and binding. We determined the structure of the AF9 AHD in complex with the elongation factor AF4 and show that aliphatic residues, which are conserved in each of the AF9 binding partners, form an integral part of the hydrophobic core of the complex. Nuclear magnetic resonance relaxation measurements show that AF9 retains significant dynamic behavior which may facilitate exchange between disordered partners. We propose that AF9 functions as a signaling hub that regulates transcription through dynamic recruitment of cofactors in normal hematopoiesis and in acute leukemia.
Chain A has been split into two chains to reflect the real biological assembly. The newly generated chain A corresponds to residues 738-779, while chain B corresponds to residues 1490-1568. Linker residues and expression tags were removed.
2
2
Other
Other
A
AF4/FMR2 family member 1
Homo sapiens
RLPLPLRDTKLLSPLRDTPPPQSLMVKITLDLLSRIPQPPGKPMG
45
P51825
738
779
3.5%
UniRef90_P51825
738
779
secondary structure
beta
763
764
pfam
PF05110.10
AF-4
8
1207
B
Protein AF-9
Homo sapiens
SDKQIKNGECDKAYLDELVELHRRLMTLRERHILQQIVNLIEETGHFHITNTTFDFDLCSLDKTTVRKLQSYLETSGTS
79
P42568
490
568
13.9%
UniRef90_P42568
490
568
secondary structure
helix
504
515
secondary structure
helix
523
531
secondary structure
beta
536
538
secondary structure
beta
543
545
secondary structure
helix
552
561
AF9 is an intrinsically disordered protein, which binds competing disordered partners, most notably AF4, Dot1L, BCoR and hPC3. The two interacting protein regions undergo mutual synergistic folding (PMID:23260655).
MF2200013
Leukemia Fusion Target AF9 in complex with hPC3
2n4q
NMR
heterodimer
Homo sapiens
Kuntimaddi, A., Leach, B.I., Bushweller, J.H.
Solution NMR Structure of CBX8 in complex with AF9 (CBX8-AF9)
To be published
-
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
2
Other
Other
A
Chromobox protein homolog 8
Homo sapiens
TQGGRPSLIARIPVARILGDPEEE
24
Q9HC52
327
349
5.9%
UniRef90_Q9HC52
327
349
secondary structure
beta
334
336
secondary structure
helix
339
342
B
Protein AF-9
Homo sapiens
MDKAYLDELVELHRRLMTLRERHILQQIVNLIEETGHFHITNTTFDFDLCSLDKTTVRKLQSYLETSGTS
70
P42568
500
568
12.1%
UniRef90_P42568
500
568
secondary structure
helix
501
514
secondary structure
helix
520
532
secondary structure
beta
537
539
secondary structure
beta
542
546
secondary structure
helix
552
563
AF9 is an intrinsically disordered protein, which binds competing disordered partners, most notably AF4, Dot1L, BCoR and hPC3. The two interacting protein regions undergo mutual synergistic folding (PMID:23260655).
MF2200014
Leukemia Fusion Target AF9 in complex with Dot1L
2mv7
NMR
heterodimer
Homo sapiens
25921540
Kuntimaddi A, Achille NJ, Thorpe J, Lokken AA, Singh R, Hemenway CS, Adli M, Zeleznik-Le NJ, Bushweller JH
Degree of Recruitment of DOT1L to MLL-AF9 Defines Level of H3K79 Di- and Tri-methylation on Target Genes and Transformation Potential.
Cell Rep
2015
5
11
808-20
The MLL gene is a common target of chromosomal translocations found in human leukemia. MLL-fusion leukemia has a consistently poor outcome. One of the most common translocation partners is AF9 (MLLT3). MLL-AF9 recruits DOT1L, a histone 3 lysine 79 methyltransferase (H3K79me1/me2/me3), leading to aberrant gene transcription. We show that DOT1L has three AF9 binding sites and present the nuclear magnetic resonance (NMR) solution structure of a DOT1L-AF9 complex. We generate structure-guided point mutations and find that they have graded effects on recruitment of DOT1L to MLL-AF9. Chromatin immunoprecipitation sequencing (ChIP-seq) analyses of H3K79me2 and H3K79me3 show that graded reduction of the DOT1L interaction with MLL-AF9 results in differential loss of H3K79me2 and me3 at MLL-AF9 target genes. Furthermore, the degree of DOT1L recruitment is linked to the level of MLL-AF9 hematopoietic transformation.
GO:0005515
protein binding
GO:0005634
nucleus
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
2
Other
Other
A
Protein AF-9
Homo sapiens
DKAYLDELVELHRRLMTLRERHILQQIVNLIEETGHFHITNTTFDFDLCSLDKTTVRKLQSYLETSGTS
69
P42568
500
568
12.1%
UniRef90_P42568
500
568
secondary structure
helix
501
516
secondary structure
helix
520
533
secondary structure
beta
537
539
secondary structure
beta
542
546
secondary structure
helix
547
549
secondary structure
helix
552
562
B
Histone-lysine N-methyltransferase, H3 lysine-79 specific
Homo sapiens
TNKLPVSIPLASVVLPSRAERARST
25
Q8TEK3
876
900
1.4%
UniRef90_Q8TEK3
877
900
secondary structure
beta
880
882
AF9 is an intrinsically disordered protein, which binds competing disordered partners, most notably AF4, Dot1L, BCoR and hPC3. The two interacting protein regions undergo mutual synergistic folding (PMID:23260655).
MF3140002
SARS-Coronavirus HR2 Domain (prefusion, trimeric form)
2fxp
NMR
homotrimer
Human SARS coronavirus
16507566
Hakansson-McReynolds S, Jiang S, Rong L, Caffrey M
Solution structure of the severe acute respiratory syndrome-coronavirus heptad repeat 2 domain in the prefusion state.
J. Biol. Chem.
2006
17
281
11965-71
The envelope glycoprotein, termed the spike protein, of severe acute respiratory syndrome coronavirus (SARS-CoV) is known to mediate viral entry. Similar to other class 1 viral fusion proteins, the heptad repeat regions of SARS-CoV spike are thought to undergo conformational changes from a prefusion form to a subsequent post-fusion form that enables fusion of the viral and host membranes. Recently, the structure of a post-fusion form of SARS-CoV spike, which consists of isolated domains of heptad repeats 1 and 2 (HR1 and HR2), has been determined by x-ray crystallography. To date there is no structural information for the prefusion conformations of SARS-CoV HR1 and HR2. In this work we present the NMR structure of the HR2 domain (residues 1141-1193) from SARS-CoV (termed S2-HR2) in the presence of the co-solvent trifluoroethanol. We find that in the absence of HR1, S2-HR2 forms a coiled coil symmetric trimer with a complex molecular mass of 18 kDa. The S2-HR2 structure, which is the first example of the prefusion form of coronavirus envelope, supports the current model of viral membrane fusion and gives insight into the design of structure-based antagonists of SARS.
GO:0046789
host cell surface receptor binding
GO:0009405
pathogenesis
GO:0046813
receptor-mediated virion attachment to host cell
GO:0039654
fusion of virus membrane with host endosome membrane
GO:0044173
host cell endoplasmic reticulum-Golgi intermediate compartment membrane
GO:0019031
viral envelope
GO:0020002
host cell plasma membrane
GO:0055036
virion membrane
GO:0016021
integral component of membrane
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
3
1
Coils and zippers
Coiled coil (trimeric)
A
Spike glycoprotein
Human SARS coronavirus
GSHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIK
55
P59594
1139
1193
4.4%
UniRef90_P59594
1140
1193
secondary structure
helix
1148
1151
secondary structure
helix
1155
1185
pfam
PF01601.13
Corona_S2
648
1252
B
Spike glycoprotein
Human SARS coronavirus
GSHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIK
55
P59594
1139
1193
4.4%
UniRef90_P59594
1140
1193
secondary structure
helix
1148
1151
secondary structure
helix
1155
1185
pfam
PF01601.13
Corona_S2
648
1252
C
Spike glycoprotein
Human SARS coronavirus
GSHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIK
55
P59594
1139
1193
4.4%
UniRef90_P59594
1140
1193
secondary structure
helix
1148
1151
secondary structure
helix
1155
1185
pfam
PF01601.13
Corona_S2
648
1252
The subunits in the structure are bound via coiled coil interactions (PMID:16507566). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
MF3100004
C-terminal coiled coil domain of Transient receptor potential (TRP) channel subfamily P member 2
3hrn
X-ray
1.90
homotrimer
Homo sapiens
19556541
Yu Y, Ulbrich MH, Li MH, Buraei Z, Chen XZ, Ong AC, Tong L, Isacoff EY, Yang J
Structural and molecular basis of the assembly of the TRPP2/PKD1 complex.
Proc. Natl. Acad. Sci. U.S.A.
2009
28
106
11558-63
Mutations in PKD1 and TRPP2 account for nearly all cases of autosomal dominant polycystic kidney disease (ADPKD). These 2 proteins form a receptor/ion channel complex on the cell surface. Using a combination of biochemistry, crystallography, and a single-molecule method to determine the subunit composition of proteins in the plasma membrane of live cells, we find that this complex contains 3 TRPP2 and 1 PKD1. A newly identified coiled-coil domain in the C terminus of TRPP2 is critical for the formation of this complex. This coiled-coil domain forms a homotrimer, in both solution and crystal structure, and binds to a single coiled-coil domain in the C terminus of PKD1. Mutations that disrupt the TRPP2 coiled-coil domain trimer abolish the assembly of both the full-length TRPP2 trimer and the TRPP2/PKD1 complex and diminish the surface expression of both proteins. These results have significant implications for the assembly, regulation, and function of the TRPP2/PKD1 complex and the pathogenic mechanism of some ADPKD-producing mutations.
GO:0048763
calcium-induced calcium release activity
GO:0005102
receptor binding
GO:0005245
voltage-gated calcium channel activity
GO:0042803
protein homodimerization activity
GO:0051371
muscle alpha-actinin binding
GO:0043398
HLH domain binding
GO:0051219
phosphoprotein binding
GO:0044325
ion channel binding
GO:0005509
calcium ion binding
GO:0005248
voltage-gated sodium channel activity
GO:0051117
ATPase binding
GO:0005267
potassium channel activity
GO:0001892
embryonic placenta development
GO:0060078
regulation of postsynaptic membrane potential
GO:0031659
positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle
GO:0072235
metanephric distal tubule development
GO:0021510
spinal cord development
GO:0045944
positive regulation of transcription from RNA polymerase II promoter
GO:0071464
cellular response to hydrostatic pressure
GO:0003127
detection of nodal flow
GO:0034614
cellular response to reactive oxygen species
GO:0051209
release of sequestered calcium ion into cytosol
GO:0072218
metanephric ascending thin limb development
GO:0072219
metanephric cortical collecting duct development
GO:0035904
aorta development
GO:0071805
potassium ion transmembrane transport
GO:0060674
placenta blood vessel development
GO:0021915
neural tube development
GO:0035502
metanephric part of ureteric bud development
GO:0007050
cell cycle arrest
GO:0001658
branching involved in ureteric bud morphogenesis
GO:0031587
positive regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity
GO:0035725
sodium ion transmembrane transport
GO:0071470
cellular response to osmotic stress
GO:0072284
metanephric S-shaped body morphogenesis
GO:0007259
JAK-STAT cascade
GO:0071498
cellular response to fluid shear stress
GO:0072177
mesonephric duct development
GO:0045429
positive regulation of nitric oxide biosynthetic process
GO:0061441
renal artery morphogenesis
GO:0071910
determination of liver left/right asymmetry
GO:0071158
positive regulation of cell cycle arrest
GO:0001947
heart looping
GO:0060315
negative regulation of ryanodine-sensitive calcium-release channel activity
GO:0072214
metanephric cortex development
GO:2000134
negative regulation of G1/S transition of mitotic cell cycle
GO:0042994
cytoplasmic sequestering of transcription factor
GO:0008285
negative regulation of cell proliferation
GO:0050982
detection of mechanical stimulus
GO:0030814
regulation of cAMP metabolic process
GO:0072075
metanephric mesenchyme development
GO:0072208
metanephric smooth muscle tissue development
GO:0051298
centrosome duplication
GO:0002133
polycystin complex
GO:0030027
lamellipodium
GO:0036064
ciliary basal body
GO:0031512
motile primary cilium
GO:0009925
basal plasma membrane
GO:0071458
integral component of cytoplasmic side of endoplasmic reticulum membrane
GO:0005911
cell-cell junction
GO:0071556
integral component of lumenal side of endoplasmic reticulum membrane
GO:0005829
cytosol
GO:0031513
nonmotile primary cilium
GO:0045180
basal cortex
GO:0060170
ciliary membrane
GO:0072686
mitotic spindle
GO:0070062
extracellular exosome
GO:0005887
integral component of plasma membrane
Chains B and C were generated from chain A using the biomatrices described in the original PDB file.
3
1
Coils and zippers
Coiled coil (trimeric)
A
Polycystin-2
Homo sapiens
MGVSYEEFQVLVRRVDRMEHSIGSIVSKIDAVIVKLEIMERAKLKRREVLGRLLDGVAEDERLG
64
Q13563
832
895
6.6%
UniRef90_Q13563
833
895
secondary structure
helix
836
894
B
Polycystin-2
Homo sapiens
MGVSYEEFQVLVRRVDRMEHSIGSIVSKIDAVIVKLEIMERAKLKRREVLGRLLDGVAEDERLG
64
Q13563
832
895
6.6%
UniRef90_Q13563
833
895
secondary structure
helix
836
894
C
Polycystin-2
Homo sapiens
MGVSYEEFQVLVRRVDRMEHSIGSIVSKIDAVIVKLEIMERAKLKRREVLGRLLDGVAEDERLG
64
Q13563
832
895
6.6%
UniRef90_Q13563
833
895
secondary structure
helix
836
894
The subunits in the structure are bound via coiled coil interactions (PMID:19556541). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
3hro
MF2110024
L27 domain complex (D. melanogaster)
4rp3
X-ray
1.36
homodimer
Drosophila melanogaster
Ghosh, A., Ramagopal, U., Ahmed, A., Bhoshle, R., Seidel, R., Stead, M., Toro, R., Almo, S.C.
Crystal Structure of the L27 Domain of Discs Large 1 (target ID NYSGRC-010766) from Drosophila melanogaster bound to a potassium ion (space group P212121)
To be published
-
GO:0004871
signal transducer activity
GO:0005154
epidermal growth factor receptor binding
GO:0005198
structural molecule activity
GO:0004385
guanylate kinase activity
GO:0035255
ionotropic glutamate receptor binding
GO:0045167
asymmetric protein localization involved in cell fate determination
GO:0042058
regulation of epidermal growth factor receptor signaling pathway
GO:0007165
signal transduction
GO:0045475
locomotor rhythm
GO:0001708
cell fate specification
GO:0045196
establishment or maintenance of neuroblast polarity
GO:0008049
male courtship behavior
GO:0045887
positive regulation of synaptic growth at neuromuscular junction
GO:0001738
morphogenesis of a polarized epithelium
GO:0007155
cell adhesion
GO:0046956
positive phototaxis
GO:0007268
synaptic transmission
GO:0019991
septate junction assembly
GO:0000122
negative regulation of transcription from RNA polymerase II promoter
GO:0030714
anterior/posterior axis specification, follicular epithelium
GO:0045197
establishment or maintenance of epithelial cell apical/basal polarity
GO:0030710
regulation of border follicle cell delamination
GO:0000132
establishment of mitotic spindle orientation
GO:0008285
negative regulation of cell proliferation
GO:0045175
basal protein localization
GO:0010906
regulation of glucose metabolic process
GO:0008593
regulation of Notch signaling pathway
GO:0043113
receptor clustering
GO:0007391
dorsal closure
GO:0046710
GDP metabolic process
GO:0097120
receptor localization to synapse
GO:0016336
establishment or maintenance of polarity of larval imaginal disc epithelium
GO:0046425
regulation of JAK-STAT cascade
GO:0007318
pole plasm protein localization
GO:0042332
gravitaxis
GO:0051124
synaptic growth at neuromuscular junction
GO:0046037
GMP metabolic process
GO:0060581
cell fate commitment involved in pattern specification
GO:0016332
establishment or maintenance of polarity of embryonic epithelium
GO:0051726
regulation of cell cycle
GO:0019233
sensory perception of pain
GO:0014069
postsynaptic density
GO:0016327
apicolateral plasma membrane
GO:0016328
lateral plasma membrane
GO:0005920
smooth septate junction
GO:0061176
type Ib terminal bouton
GO:0016323
basolateral plasma membrane
GO:0005856
cytoskeleton
GO:0048471
perinuclear region of cytoplasm
GO:0045179
apical cortex
GO:0045211
postsynaptic membrane
GO:0031594
neuromuscular junction
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
L27 domains
L27_1 type
A
Disks large 1 tumor suppressor protein
Drosophila melanogaster
SMPVKKQEAHRALELLEDYHARLSEPQDRALRIAIERVIRIFKSRLFQALLDIQEFYELTLLDDSKSIQQKTAETLQIATKWEKDGQAVKIADFIKSS
98
P31007
1
97
10%
UniRef90_P31007
1
97
secondary structure
helix
8
21
secondary structure
helix
25
60
secondary structure
helix
67
86
secondary structure
beta
87
90
pfam
PF09058.7
L27_1
4
62
B
Disks large 1 tumor suppressor protein
Drosophila melanogaster
SMPVKKQEAHRALELLEDYHARLSEPQDRALRIAIERVIRIFKSRLFQALLDIQEFYELTLLDDSKSIQQKTAETLQIATKWEKDGQAVKIADFIKSS
98
P31007
1
97
10%
UniRef90_P31007
1
97
secondary structure
helix
8
21
secondary structure
helix
25
60
secondary structure
helix
67
86
secondary structure
beta
88
92
pfam
PF09058.7
L27_1
4
62
The interacting chains form half of a heterotetrameric L27 complex (a dimer of dimers) (PMID:16147993). L27 complexes formed by Lin-2 and Lin-7 proteins were shown to function as obligate heterodimers/tetramers undergoing a cooperative unfolding transition. Circular dichroism studies reveal that the individual monomers are largely unfolded outside the complex form (PMID:12110687).
4rp4
4rp5
MF2110025
Tropomyosin dimer (Gallus gallus)
1ic2
X-ray
2.00
homodimer
Gallus gallus
11438684
Brown JH, Kim KH, Jun G, Greenfield NJ, Dominguez R, Volkmann N, Hitchcock-DeGregori SE, Cohen C
Deciphering the design of the tropomyosin molecule.
Proc. Natl. Acad. Sci. U.S.A.
2001
15
98
8496-501
The crystal structure at 2.0-A resolution of an 81-residue N-terminal fragment of muscle alpha-tropomyosin reveals a parallel two-stranded alpha-helical coiled-coil structure with a remarkable core. The high alanine content of the molecule is clustered into short regions where the local 2-fold symmetry is broken by a small (approximately 1.2-A) axial staggering of the helices. The joining of these regions with neighboring segments, where the helices are in axial register, gives rise to specific bends in the molecular axis. We observe such bends to be widely distributed in two-stranded alpha-helical coiled-coil proteins. This asymmetric design in a dimer of identical (or highly similar) sequences allows the tropomyosin molecule to adopt multiple bent conformations. The seven alanine clusters in the core of the complete molecule (which spans seven monomers of the actin helix) promote the semiflexible winding of the tropomyosin filament necessary for its regulatory role in muscle contraction.
GO:0003779
actin binding
GO:0005886
plasma membrane
GO:0005856
cytoskeleton
GO:0005737
cytoplasm
Chains C and D were removed as chains A and B represent the biologically relevant dimer.
2
1
Coils and zippers
Coiled coil (dimeric)
A
Tropomyosin alpha-1 chain
Gallus gallus
MDAIKKKMQMLKLDKENALDRAEQAEADKKAAEERSKQLEDELVALQKKLKGTEDELDKYSESLKDAQEKLELADKKATDC
81
P04268
1
81
28.5%
UniRef90_P09493
1
81
secondary structure
helix
3
77
pfam
PF00261.17
Tropomyosin
48
284
B
Tropomyosin alpha-1 chain
Gallus gallus
MDAIKKKMQMLKLDKENALDRAEQAEADKKAAEERSKQLEDELVALQKKLKGTEDELDKYSESLKDAQEKLELADKKATDC
81
P04268
1
81
28.5%
UniRef90_P09493
1
81
secondary structure
helix
3
75
pfam
PF00261.17
Tropomyosin
48
284
The subunits in the structure are bound via coiled coil interactions (PMID:11438684). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
3mtu
3u1a
3u1c
1c1g
MF2110026
N-Terminal dimerization domain Lis1
1uuj
X-ray
1.75
homodimer
Rattus norvegicus
15274919
Kim MH, Cooper DR, Oleksy A, Devedjiev Y, Derewenda U, Reiner O, Otlewski J, Derewenda ZS
The structure of the N-terminal domain of the product of the lissencephaly gene Lis1 and its functional implications.
Structure
2004
6
12
987-98
Mutations in the Lis1 gene result in lissencephaly (smooth brain), a debilitating developmental syndrome caused by the impaired ability of postmitotic neurons to migrate to their correct destination in the cerebral cortex. Sequence similarities suggest that the LIS1 protein contains a C-terminal seven-blade beta-propeller domain, while the structure of the N-terminal fragment includes the LisH (Lis-homology) motif, a pattern found in over 100 eukaryotic proteins with a hitherto unknown function. We present the 1.75 A resolution crystal structure of the N-terminal domain of mouse LIS1, and we show that the LisH motif is a novel, thermodynamically very stable dimerization domain. The structure explains the molecular basis of a low severity form of lissencephaly.
GO:0008017
microtubule binding
GO:0042803
protein homodimerization activity
GO:0051219
phosphoprotein binding
GO:0045505
dynein intermediate chain binding
GO:0047179
platelet-activating factor acetyltransferase activity
GO:0007268
synaptic transmission
GO:0050885
neuromuscular process controlling balance
GO:0042249
establishment of planar polarity of embryonic epithelium
GO:0090102
cochlea development
GO:0051081
nuclear envelope disassembly
GO:0045773
positive regulation of axon extension
GO:0021819
layer formation in cerebral cortex
GO:0061003
positive regulation of dendritic spine morphogenesis
GO:0001961
positive regulation of cytokine-mediated signaling pathway
GO:0001667
ameboidal-type cell migration
GO:0007405
neuroblast proliferation
GO:0017145
stem cell division
GO:0045931
positive regulation of mitotic cell cycle
GO:0090176
microtubule cytoskeleton organization involved in establishment of planar polarity
GO:0043622
cortical microtubule organization
GO:0046329
negative regulation of JNK cascade
GO:0030036
actin cytoskeleton organization
GO:0040019
positive regulation of embryonic development
GO:0007097
nuclear migration
GO:0001675
acrosome assembly
GO:0043087
regulation of GTPase activity
GO:0051660
establishment of centrosome localization
GO:0048854
brain morphogenesis
GO:0008090
retrograde axonal transport
GO:0021540
corpus callosum morphogenesis
GO:0016042
lipid catabolic process
GO:0021895
cerebral cortex neuron differentiation
GO:0021766
hippocampus development
GO:0019226
transmission of nerve impulse
GO:2000574
regulation of microtubule motor activity
GO:0000132
establishment of mitotic spindle orientation
GO:0009306
protein secretion
GO:0007611
learning or memory
GO:0010977
negative regulation of neuron projection development
GO:0070507
regulation of microtubule cytoskeleton organization
GO:0007067
mitotic nuclear division
GO:0031023
microtubule organizing center organization
GO:0001764
neuron migration
GO:0047496
vesicle transport along microtubule
GO:0008344
adult locomotory behavior
GO:0036035
osteoclast development
GO:0060117
auditory receptor cell development
GO:0031512
motile primary cilium
GO:0005813
centrosome
GO:0031965
nuclear membrane
GO:0031252
cell leading edge
GO:0000235
astral microtubule
GO:1904115
axon cytoplasm
GO:0005938
cell cortex
GO:0005829
cytosol
GO:0005871
kinesin complex
GO:0043025
neuronal cell body
GO:0030426
growth cone
GO:0048471
perinuclear region of cytoplasm
GO:0000776
kinetochore
GO:0070062
extracellular exosome
Chains C and D were removed as chains A and B represent the biologically relevant dimer.
2
1
Other
Other
A
Platelet-activating factor acetylhydrolase IB subunit alpha
Rattus norvegicus
GAMVLSQRQRDELNRAIADYLRSNGYEEAYSVFKKEAELDMNEELDKKYAGLLEKKWTSVIRLQKKVMELESKLNEAKEEFTSGGPLG
88
P63004
1
86
21%
UniRef90_P63005
1
86
secondary structure
helix
5
21
secondary structure
helix
25
34
secondary structure
helix
42
48
secondary structure
helix
51
56
secondary structure
helix
59
65
secondary structure
helix
67
76
pfam
PF08513.8
LisH
9
35
B
Platelet-activating factor acetylhydrolase IB subunit alpha
Rattus norvegicus
GAMVLSQRQRDELNRAIADYLRSNGYEEAYSVFKKEAELDMNEELDKKYAGLLEKKWTSVIRLQKKVMELESKLNEAKEEFTSGGPLG
88
P63004
1
86
21%
UniRef90_P63005
1
86
secondary structure
helix
5
21
secondary structure
helix
25
34
secondary structure
helix
42
48
secondary structure
helix
51
65
secondary structure
helix
67
75
pfam
PF08513.8
LisH
9
35
Lis1 was shown to be a dimer under native conditions. Monitoring the chemically induced unfolding of the protein by fluorescence and by circular dichroism revealed that the reaction follows a single and coincident transition.
MF2110027
Mannose-binding lectin (Hyacinthoides hispanica)
1b2p
X-ray
1.70
homodimer
Hyacinthoides hispanica
10393293
Wood SD, Wright LM, Reynolds CD, Rizkallah PJ, Allen AK, Peumans WJ, Van Damme EJ
Structure of the native (unligated) mannose-specific bulb lectin from Scilla campanulata (bluebell) at 1.7 A resolution.
Acta Crystallogr. D Biol. Crystallogr.
1999
Pt 7
55
1264-72
The X-ray crystal structure of native Scilla campanulata agglutinin, a mannose-specific lectin from bluebell bulbs and a member of the Liliaceae family, has been determined by molecular replacement and refined to an R value of 0.186 at 1.7 A resolution. The lectin crystallizes in space group P21212 with unit-cell parameters a = 70. 42, b = 92.95, c = 46.64 A. The unit cell contains eight protein molecules of Mr = 13143 Da (119 amino-acid residues). The asymmetric unit comprises two chemically identical molecules, A and B, related by a non-crystallographic twofold axis perpendicular to c. This dimer further associates by crystallographic twofold symmetry to form a tetramer. The fold of the polypeptide backbone closely resembles that found in the lectins from Galanthus nivalis (snowdrop) and Hippeastrum (amaryllis) and contains a threefold symmetric beta-prism made up of three antiparallel four-stranded beta-sheets. Each of the four-stranded beta-sheets (I, II and III) possesses a potential saccharide-binding site containing conserved residues; however, site II has two mutations relative to sites I and III which may prevent ligation at this site. Our study provides the first accurate and detailed description of a native (unligated) structure from this superfamily of mannose-specific bulb lectins and will allow comparisons with a number of lectin-saccharide complexes which have already been determined or are currently under investigation.
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Bulb-type lectin domain
Homodimeric lectin
A
Lectin SCAman (Fragment)
Hyacinthoides hispanica
NNIIFSKQPDDNHPQILHATESLEILFGTHVYRFIMQTDCNLVLYDNNNPIWATNTGGLGNGCRAVLQPDGVLVVITNENVTVWQSPVAGKAGHYVLVLQPDRNVVIYGDALWATQTVR
119
Q9ZP49
22
140
76.8%
UniRef90_Q9ZP49
22
140
secondary structure
beta
24
26
secondary structure
beta
37
39
secondary structure
beta
43
48
secondary structure
beta
51
57
secondary structure
beta
63
67
secondary structure
beta
70
74
secondary structure
beta
85
88
secondary structure
beta
94
97
secondary structure
beta
103
106
secondary structure
beta
116
120
secondary structure
beta
126
130
secondary structure
beta
132
135
pfam
PF01453.21
B_lectin
35
112
B
Lectin SCAman (Fragment)
Hyacinthoides hispanica
NNIIFSKQPDDNHPQILHATESLEILFGTHVYRFIMQTDCNLVLYDNNNPIWATNTGGLGNGCRAVLQPDGVLVVITNENVTVWQSPVAGKAGHYVLVLQPDRNVVIYGDALWATQTVR
119
Q9ZP49
22
140
76.8%
UniRef90_Q9ZP49
22
140
secondary structure
beta
24
26
secondary structure
beta
37
39
secondary structure
beta
43
48
secondary structure
beta
51
57
secondary structure
beta
63
67
secondary structure
beta
70
74
secondary structure
beta
85
88
secondary structure
beta
94
97
secondary structure
beta
103
106
secondary structure
beta
116
120
secondary structure
beta
126
130
secondary structure
beta
132
135
pfam
PF01453.21
B_lectin
35
112
A closely homologous lectin of the same type sharing a high degree of sequence and structural similarity has been shown to follow a two-state folding process (PMID:11401577).
MF2110028
Dimerization domain of the type I alpha regulatory subunit of protein kinase A
2ezw
NMR
homodimer
Bos taurus
12860132
Banky P, Roy M, Newlon MG, Morikis D, Haste NM, Taylor SS, Jennings PA
Related protein-protein interaction modules present drastically different surface topographies despite a conserved helical platform.
J. Mol. Biol.
2003
5
330
1117-29
The subcellular localization of cAMP-dependent protein kinase (PKA) occurs through interaction with A-Kinase Anchoring Proteins (AKAPs). AKAPs bind to the PKA regulatory subunit dimer of both type Ialpha and type IIalpha (RIalpha and RIIalpha). RIalpha and RIIalpha display characteristic localization within different cell types, which is maintained by interaction of AKAPs with the N-terminal dimerization and docking domain (D/D) of the respective regulatory subunit. Previously, we reported the solution structure of RIIa D/D module, both free and bound to AKAPs. We have now solved the solution structure of the dimerization and docking domain of the type Ialpha regulatory dimer subunit (RIalpha D/D). RIalpha D/D is a compact docking module, with unusual interchain disulfide bonds that help maintain the AKAP interaction surface. In contrast to the shallow hydrophobic groove for AKAP binding across the surface of the RIIalpha D/D dimeric interface, the RIalpha D/D module presents a deep cleft for proposed AKAP binding. RIalpha and RIIalpha D/D interaction modules present drastically differing dimeric topographies, despite a conserved X-type four-helix bundle structure.
GO:0031625
ubiquitin protein ligase binding
GO:0004862
cAMP-dependent protein kinase inhibitor activity
GO:0034236
protein kinase A catalytic subunit binding
GO:0008603
cAMP-dependent protein kinase regulator activity
GO:0030552
cAMP binding
GO:2000480
negative regulation of cAMP-dependent protein kinase activity
GO:0060038
cardiac muscle cell proliferation
GO:0046007
negative regulation of activated T cell proliferation
GO:0001707
mesoderm formation
GO:0045214
sarcomere organization
GO:0044853
plasma membrane raft
GO:0005737
cytoplasm
GO:0031588
nucleotide-activated protein kinase complex
GO:0031594
neuromuscular junction
GO:0001772
immunological synapse
GO:0005952
cAMP-dependent protein kinase complex
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Other
Other
A
cAMP-dependent protein kinase type I-alpha regulatory subunit
Bos taurus
SLRECELYVQKHNIQALLKDSIVQLCTARPERPMAFLREYFEKLEKEEAK
50
P00514
13
62
13.2%
UniRef90_P10644
14
63
secondary structure
helix
14
17
secondary structure
helix
27
37
secondary structure
helix
45
57
pfam
PF02197.14
RIIa
24
61
B
cAMP-dependent protein kinase type I-alpha regulatory subunit
Bos taurus
SLRECELYVQKHNIQALLKDSIVQLCTARPERPMAFLREYFEKLEKEEAK
50
P00514
13
62
13.2%
UniRef90_P10644
14
63
secondary structure
helix
14
17
secondary structure
helix
27
37
secondary structure
helix
45
57
pfam
PF02197.14
RIIa
24
61
A
The N-terminal dimerization region of RIalpha is highly mobile evading structure determination by X-ray (PMID:24316401).
B
The N-terminal dimerization region of RIalpha is highly mobile evading structure determination by X-ray (PMID:24316401).
3im3
3im4
5hvz
MF2110029
Coiled Coil Domain of Pawr
5fiy
X-ray
3.00
homodimer
Rattus norvegicus
Tiruttani Subhramanyam, U.K., Kubicek, J., Eidhoff, U.B., Labahn, J.
The Structure of Coiled Coil Domain of Pawr
To be published
-
Chains C, D, E, F and G were removed as chains A and B represent the biologically relevant dimer.
2
1
Coils and zippers
Coiled coil (dimeric)
A
PRKC apoptosis WT1 regulator protein
Rattus norvegicus
ASWSHPQFEKAGFSRHNRDTSAPANFASSSTLEKRIEDLEKEVLRERQENLRLTRLMQDKEEMIGKLKEEIDLLNRDLDDMEDENEQLKQENKTLLKVVGQLTR
104
Q62627
240
332
28%
UniRef90_Q62627
240
332
secondary structure
helix
257
284
secondary structure
helix
286
290
secondary structure
helix
292
308
secondary structure
helix
310
331
B
PRKC apoptosis WT1 regulator protein
Rattus norvegicus
ASWSHPQFEKAGFSRHNRDTSAPANFASSSTLEKRIEDLEKEVLRERQENLRLTRLMQDKEEMIGKLKEEIDLLNRDLDDMEDENEQLKQENKTLLKVVGQLTR
104
Q62627
240
332
28%
UniRef90_Q62627
240
332
secondary structure
helix
257
284
secondary structure
helix
286
290
secondary structure
helix
292
308
secondary structure
helix
310
332
The subunits in the structure are bound via coiled coil interactions. Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
MF4110009
p53/p73-b homo-tetramerization domain (Ciona intestinalis)
2mw4
NMR
homotetramer (dimer of dimers)
Ciona intestinalis
26473758
Heering J, Jonker HR, Löhr F, Schwalbe H, Dötsch V
Structural investigations of the p53/p73 homologs from the tunicate species Ciona intestinalis reveal the sequence requirements for the formation of a tetramerization domain.
Protein Sci.
2015
Most members of the p53 family of transcription factors form tetramers. Responsible for determining the oligomeric state is a short oligomerization domain consisting of one β-strand and one α-helix. With the exception of human p53 all other family members investigated so far contain a second α-helix as part of their tetramerization domain. Here we have used NMR spectroscopy to characterize the oligomerization domains of the two p53-like proteins from the tunicate Ciona intestinalis, representing the closest living relative of vertebrates. Structure determination reveals for one of the two proteins a new type of packing of this second α-helix on the core domain that was not predicted based on the sequence, while the other protein does not form a second helix despite the presence of crucial residues that are conserved in all other family members that form a second helix. By mutational analysis we identify a proline as well as large hydrophobic residues in the hinge region between both helices as the crucial determinant for the formation of a second helix. This article is protected by copyright. All rights reserved.
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
1
Other
p53 tetramerization
A
Uncharacterized protein
Ciona intestinalis
SDGDVVYTLNIRGKRKFEKVKEYKEALDLLDYVQPDVKKACCQRNQI
47
F6SSG7
374
419
11%
UniRef90_F6SSG7
374
419
secondary structure
beta
378
384
secondary structure
helix
386
402
secondary structure
helix
407
414
pfam
PF07710.8
P53_tetramer
367
408
B
Uncharacterized protein
Ciona intestinalis
SDGDVVYTLNIRGKRKFEKVKEYKEALDLLDYVQPDVKKACCQRNQI
47
F6SSG7
374
419
11%
UniRef90_F6SSG7
374
419
secondary structure
beta
378
384
secondary structure
helix
386
402
secondary structure
helix
407
417
pfam
PF07710.8
P53_tetramer
367
408
C
Uncharacterized protein
Ciona intestinalis
SDGDVVYTLNIRGKRKFEKVKEYKEALDLLDYVQPDVKKACCQRNQI
47
F6SSG7
374
419
11%
UniRef90_F6SSG7
374
419
secondary structure
beta
378
384
secondary structure
helix
386
402
secondary structure
helix
407
414
pfam
PF07710.8
P53_tetramer
367
408
D
Uncharacterized protein
Ciona intestinalis
SDGDVVYTLNIRGKRKFEKVKEYKEALDLLDYVQPDVKKACCQRNQI
47
F6SSG7
374
419
11%
UniRef90_F6SSG7
374
419
secondary structure
beta
378
384
secondary structure
helix
386
402
secondary structure
helix
407
414
pfam
PF07710.8
P53_tetramer
367
408
p53, p63, p73 and their homologues are all members of the p53 protein family. The tetramerization region of p53, p63 and p73 are closely homologous to each other, having very similar sequences, structures and biological functions (PMID:25185827, PMID:18289041, PMID:20379196), all containing the same Pfam domain (PF07710). The tetramerization domain of p53 exhibits a four-helix bundle structure bound by hydrophobic and electrostatic interactions (PMID:8023159). The tetramer is formed as a dimer of dimers and follows a two state folding and binding process, demonstrated in several chemical and thermal denaturation/refolding experiments (PMID:9582268, PMID:18410249, PMID:19913028).
MF6240001
Human respiratory syncytial virus fusion protein core
1g2c
X-ray
2.30
heterohexamer
Human respiratory syncytial virus A
11106388
Zhao X, Singh M, Malashkevich VN, Kim PS
Structural characterization of the human respiratory syncytial virus fusion protein core.
Proc. Natl. Acad. Sci. U.S.A.
2000
26
97
14172-7
Human respiratory syncytial virus (HRSV) is a major cause of a number of severe respiratory diseases, including bronchiolitis and pneumonia, in infants and young children. The HRSV F protein, a glycoprotein essential for viral entry, is a primary target for vaccine and drug development. Two heptad-repeat regions within the HRSV F sequence were predicted by the computer program learncoil-vmf. These regions are thought to form trimer-of-hairpins-like structures, similar to those found in the fusion proteins of several enveloped viruses. The hairpin structure likely brings the viral and cellular membranes into close apposition, thereby facilitating membrane fusion and subsequent viral entry. Here, we show that peptides, denoted HR-N and HR-C, corresponding to the heptad-repeat regions from the N-terminal and C-terminal segments of the HRSV F protein, respectively, form a stable alpha-helical trimer of heterodimers. The HRSV N/C complex was crystallized and its x-ray structure was determined at 2.3-A resolution. As anticipated, the complex is a six-helix bundle in which the HR-N peptides form a three-stranded, central coiled coil, and the HR-C peptides pack in an antiparallel manner into hydrophobic grooves on the coiled-coil surface. There is remarkable structural similarity between the HRSV N/C complex and the fusion protein core of other viruses, including HIV-1 gp41. In addition, earlier work has shown that HRSV HR-C peptides, like the HIV-1 gp41 C peptides, inhibit viral infection. Thus, drug discovery and vaccine development strategies aimed at inhibiting viral entry by blocking hairpin formation may be applied to the inhibition of HRSV.
GO:0019064
fusion of virus membrane with host plasma membrane
GO:0060141
positive regulation of syncytium formation by virus
GO:0019031
viral envelope
GO:0055036
virion membrane
GO:0020002
host cell plasma membrane
GO:0016021
integral component of membrane
Chains G, H, I, J, K, L, M, N, O, P, Q, R, S, T, U, V, W and X were removed as chains A, B, C, D, E and F represent the biologically relevant dimer.
6
2
Coils and zippers
Coiled coil (hexameric)
A
Fusion glycoprotein F0
Human respiratory syncytial virus A
LHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNK
52
P11209
158
209
9.1%
UniRef90_P03420
158
209
secondary structure
helix
161
164
secondary structure
helix
166
208
pfam
PF00523.15
Fusion_gly
29
541
B
Fusion glycoprotein F0
Human respiratory syncytial virus A
FYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAG
43
P11209
477
519
7.5%
UniRef90_P03420
477
519
secondary structure
helix
485
513
pfam
PF00523.15
Fusion_gly
29
541
C
Fusion glycoprotein F0
Human respiratory syncytial virus A
LHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNK
52
P11209
158
209
9.1%
UniRef90_P03420
158
209
secondary structure
helix
161
206
pfam
PF00523.15
Fusion_gly
29
541
D
Fusion glycoprotein F0
Human respiratory syncytial virus A
FYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAG
43
P11209
477
519
7.5%
UniRef90_P03420
477
519
secondary structure
helix
487
514
pfam
PF00523.15
Fusion_gly
29
541
E
Fusion glycoprotein F0
Human respiratory syncytial virus A
LHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNK
52
P11209
158
209
9.1%
UniRef90_P03420
158
209
secondary structure
helix
161
206
pfam
PF00523.15
Fusion_gly
29
541
F
Fusion glycoprotein F0
Human respiratory syncytial virus A
FYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAG
43
P11209
477
519
7.5%
UniRef90_P03420
477
519
secondary structure
helix
485
514
pfam
PF00523.15
Fusion_gly
29
541
The subunits in the structure are bound via coiled coil interactions (PMID:11106388). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
3kpe
3rrr
3rrt
4jhw
4zyp
5j3d
5toj
5tok
5u68
MF4140003
Measles virus phosphoprotein tetramerization domain
4bhv
X-ray
2.10
homotetramer
Measles virus
24914970
Blocquel D, Habchi J, Durand E, Sevajol M, Ferron F, Erales J, Papageorgiou N, Longhi S
Coiled-coil deformations in crystal structures: the measles virus phosphoprotein multimerization domain as an illustrative example.
Acta Crystallogr. D Biol. Crystallogr.
2014
Pt 6
70
1589-603
The structures of two constructs of the measles virus (MeV) phosphoprotein (P) multimerization domain (PMD) are reported and are compared with a third structure published recently by another group [Communie et al. (2013), J. Virol. 87, 7166-7169]. Although the three structures all have a tetrameric and parallel coiled-coil arrangement, structural comparison unveiled considerable differences in the quaternary structure and unveiled that the three structures suffer from significant structural deformation induced by intermolecular interactions within the crystal. These results show that crystal packing can bias conclusions about function and mechanism based on analysis of a single crystal structure, and they challenge to some extent the assumption according to which coiled-coil structures can be reliably predicted from the amino-acid sequence. Structural comparison also highlighted significant differences in the extent of disorder in the C-terminal region of each monomer. The differential flexibility of the C-terminal region is also supported by size-exclusion chromatography and small-angle X-ray scattering studies, which showed that MeV PMD exists in solution as a dynamic equilibrium between two tetramers of different compaction. Finally, the possible functional implications of the flexibility of the C-terminal region of PMD are discussed.
GO:0003968
RNA-directed RNA polymerase activity
GO:0003723
RNA binding
GO:0005515
protein binding
GO:0001172
transcription, RNA-templated
GO:0006351
transcription, DNA-templated
GO:0019079
viral genome replication
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
4
1
Coils and zippers
Coiled coil (tetrameric)
A
Phosphoprotein
Measles virus
MGDHYDDELFSDVQDIKTALAKIHEDNQKIISKLESLLLLKGEVESIKKQINRQNISIHHHHHH
64
P03422
304
360
11.2%
UniRef90_P35974
304
360
secondary structure
helix
309
340
secondary structure
helix
342
360
pfam
PF03210.10
Paramyx_P_V_C
324
502
B
Phosphoprotein
Measles virus
MGDHYDDELFSDVQDIKTALAKIHEDNQKIISKLESLLLLKGEVESIKKQINRQNISIHHHHHH
64
P03422
304
360
11.2%
UniRef90_P35974
304
360
secondary structure
helix
311
360
pfam
PF03210.10
Paramyx_P_V_C
324
502
C
Phosphoprotein
Measles virus
MGDHYDDELFSDVQDIKTALAKIHEDNQKIISKLESLLLLKGEVESIKKQINRQNISIHHHHHH
64
P03422
304
360
11.2%
UniRef90_P35974
304
360
secondary structure
helix
309
340
secondary structure
helix
342
360
pfam
PF03210.10
Paramyx_P_V_C
324
502
D
Phosphoprotein
Measles virus
MGDHYDDELFSDVQDIKTALAKIHEDNQKIISKLESLLLLKGEVESIKKQINRQNISIHHHHHH
64
P03422
304
360
11.2%
UniRef90_P35974
304
360
secondary structure
helix
309
340
secondary structure
helix
342
360
pfam
PF03210.10
Paramyx_P_V_C
324
502
The subunits in the structure are bound via coiled coil interactions (PMID:23576502). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
4c5q
3zdo
MF4140004
Core (C) protein from West Nile Virus
1sfk
X-ray
3.20
homotetramer
Kunjin virus
15242592
Dokland T, Walsh M, Mackenzie JM, Khromykh AA, Ee KH, Wang S
West Nile virus core protein; tetramer structure and ribbon formation.
Structure
2004
7
12
1157-63
We have determined the crystal structure of the core (C) protein from the Kunjin subtype of West Nile virus (WNV), closely related to the NY99 strain of WNV, currently a major health threat in the U.S. WNV is a member of the Flaviviridae family of enveloped RNA viruses that contains many important human pathogens. The C protein is associated with the RNA genome and forms the internal core which is surrounded by the envelope in the virion. The C protein structure contains four alpha helices and forms dimers that are organized into tetramers. The tetramers form extended filamentous ribbons resembling the stacked alpha helices seen in HEAT protein structures.
GO:0005198
structural molecule activity
GO:0004252
serine-type endopeptidase activity
GO:0005524
ATP binding
GO:0004483
mRNA (nucleoside-2'-O-)-methyltransferase activity
GO:0003724
RNA helicase activity
GO:0046983
protein dimerization activity
GO:0070008
serine-type exopeptidase activity
GO:0003968
RNA-directed RNA polymerase activity
GO:0003725
double-stranded RNA binding
GO:0004482
mRNA (guanine-N7-)-methyltransferase activity
GO:0008026
ATP-dependent helicase activity
GO:0046872
metal ion binding
GO:0080009
mRNA methylation
GO:0039574
suppression by virus of host TYK2 activity
GO:0039520
induction by virus of host autophagy
GO:0006355
regulation of transcription, DNA-templated
GO:0039694
viral RNA genome replication
GO:0019062
virion attachment to host cell
GO:0075512
clathrin-mediated endocytosis of virus by host cell
GO:0039576
suppression by virus of host JAK1 activity
GO:0001172
transcription, RNA-templated
GO:0006370
7-methylguanosine mRNA capping
GO:0039502
suppression by virus of host type I interferon-mediated signaling pathway
GO:0036265
RNA (guanine-N7)-methylation
GO:0006351
transcription, DNA-templated
GO:0006508
proteolysis
GO:0039654
fusion of virus membrane with host endosome membrane
GO:0005576
extracellular region
GO:0019028
viral capsid
GO:0016021
integral component of membrane
GO:0044167
host cell endoplasmic reticulum membrane
GO:0042025
host cell nucleus
GO:0055036
virion membrane
GO:0019031
viral envelope
Chains E, F, G and H were removed as chains A, B, C and D represent the biologically relevant dimer.
4
1
Other
Other
A
Genome polyprotein
Kunjin virus
RVLSLTGLKRAMLSLIDGRGPTRFVLALLAFFRFTAIAPTRAVLDRWRSVNKQTAMKHLLSFKKELGTLTSAINRR
76
P14335
23
98
2.2%
UniRef90_P06935
23
98
secondary structure
helix
26
38
secondary structure
helix
44
56
secondary structure
helix
63
69
secondary structure
helix
74
95
pfam
PF01003.16
Flavi_capsid
6
123
B
Genome polyprotein
Kunjin virus
RVLSLTGLKRAMLSLIDGRGPTRFVLALLAFFRFTAIAPTRAVLDRWRSVNKQTAMKHLLSFKKELGTLTSAINRR
76
P14335
23
98
2.2%
UniRef90_P06935
23
98
secondary structure
helix
44
56
secondary structure
helix
63
69
secondary structure
helix
74
95
pfam
PF01003.16
Flavi_capsid
6
123
C
Genome polyprotein
Kunjin virus
RVLSLTGLKRAMLSLIDGRGPTRFVLALLAFFRFTAIAPTRAVLDRWRSVNKQTAMKHLLSFKKELGTLTSAINRR
76
P14335
23
98
2.2%
UniRef90_P06935
23
98
secondary structure
helix
31
37
secondary structure
helix
44
56
secondary structure
helix
63
69
secondary structure
helix
74
95
pfam
PF01003.16
Flavi_capsid
6
123
D
Genome polyprotein
Kunjin virus
RVLSLTGLKRAMLSLIDGRGPTRFVLALLAFFRFTAIAPTRAVLDRWRSVNKQTAMKHLLSFKKELGTLTSAINRR
76
P14335
23
98
2.2%
UniRef90_P06935
23
98
secondary structure
helix
26
38
secondary structure
helix
44
56
secondary structure
helix
63
69
secondary structure
helix
74
95
pfam
PF01003.16
Flavi_capsid
6
123
A
The 1-105 region described in DisProt entry DP00673 covers 100% of the sequence present in the structure.
B
The 1-105 region described in DisProt entry DP00673 covers 100% of the sequence present in the structure.
C
The 1-105 region described in DisProt entry DP00673 covers 100% of the sequence present in the structure.
D
The 1-105 region described in DisProt entry DP00673 covers 100% of the sequence present in the structure.
MF2100017
C-terminal domain of the end-binding protein 1 (EB1)
1wu9
X-ray
1.54
homodimer
Homo sapiens
15616574
Honnappa S, John CM, Kostrewa D, Winkler FK, Steinmetz MO
Structural insights into the EB1-APC interaction.
EMBO J.
2005
2
24
261-9
EB1 proteins bind to microtubule ends where they act in concert with other components, including the adenomatous polyposis coli (APC) tumor suppressor, to regulate the microtubule filament system. We find that EB1 is a stable dimer with a parallel coiled coil and show that dimerization is essential for the formation of its C-terminal domain (EB1-C). The crystal structure of EB1-C reveals a highly conserved surface patch with a deep hydrophobic cavity at its center. EB1-C binds two copies of an APC-derived C-terminal peptide (C-APCp1) with equal 5 microM affinity. The conserved APC Ile2805-Pro2806 sequence motif serves as an anchor for the interaction of C-APCp1 with the hydrophobic cavity of EB1-C. Phosphorylation of the conserved Cdc2 site Ser2789-Lys2792 in C-APCp1 reduces binding four-fold, indicating that the interaction APC-EB1 is post-translationally regulated in cells. Our findings provide a basis for understanding the dynamic crosstalk of EB1 proteins with their molecular targets in eukaryotic organisms.
GO:0044822
poly(A) RNA binding
GO:0042802
identical protein binding
GO:0098641
cadherin binding involved in cell-cell adhesion
GO:0008022
protein C-terminus binding
GO:0051010
microtubule plus-end binding
GO:0031115
negative regulation of microtubule polymerization
GO:0007062
sister chromatid cohesion
GO:0035372
protein localization to microtubule
GO:0008283
cell proliferation
GO:1903033
positive regulation of microtubule plus-end binding
GO:0051301
cell division
GO:1904527
negative regulation of microtubule binding
GO:0007067
mitotic nuclear division
GO:0000086
G2/M transition of mitotic cell cycle
GO:0098609
cell-cell adhesion
GO:0030335
positive regulation of cell migration
GO:0030981
cortical microtubule cytoskeleton
GO:0005829
cytosol
GO:0005913
cell-cell adherens junction
GO:0035371
microtubule plus-end
GO:0005813
centrosome
GO:0005794
Golgi apparatus
GO:0031253
cell projection membrane
GO:0005881
cytoplasmic microtubule
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Coils and zippers
Coiled coil (dimeric)
A
Microtubule-associated protein RP/EB family member 1
Homo sapiens
GSDEAAELMQQVNVLKLTVEDLEKERDFYFGKLRNIELICQENEGENDPVLQRIVDILYATDEGFVIPDEGGPQEEQEEY
80
Q15691
189
268
29.9%
UniRef90_Q15691
189
268
secondary structure
helix
192
230
secondary structure
helix
237
247
pfam
PF03271.14
EB1
210
248
B
Microtubule-associated protein RP/EB family member 1
Homo sapiens
GSDEAAELMQQVNVLKLTVEDLEKERDFYFGKLRNIELICQENEGENDPVLQRIVDILYATDEGFVIPDEGGPQEEQEEY
80
Q15691
189
268
29.9%
UniRef90_Q15691
189
268
secondary structure
helix
192
230
secondary structure
helix
237
249
secondary structure
helix
251
253
pfam
PF03271.14
EB1
210
248
EB1 is a stable dimer with a parallel coiled coil and show that dimerization is essential for the formation of its C-terminal domain (EB1-C) (PMID:15616574).
1txq
1yib
1yig
2hkq
2hl5
2r8u
3gjo
3tq7
4xa3
4xa6
5jv3
5jvm
5jvp
5jvr
5jvs
5jvu
5jx1
MF6140001
SARS-Coronavirus HR2 Domain (post-fusion, hexameric form)
1zv8
X-ray
1.94
homohexamer
Human SARS coronavirus
16698550
Deng Y, Liu J, Zheng Q, Yong W, Lu M
Structures and polymorphic interactions of two heptad-repeat regions of the SARS virus S2 protein.
Structure
2006
5
14
889-99
Entry of SARS coronavirus into its target cell requires large-scale structural transitions in the viral spike (S) glycoprotein in order to induce fusion of the virus and cell membranes. Here we describe the identification and crystal structures of four distinct alpha-helical domains derived from the highly conserved heptad-repeat (HR) regions of the S2 fusion subunit. The four domains are an antiparallel four-stranded coiled coil, a parallel trimeric coiled coil, a four-helix bundle, and a six-helix bundle that is likely the final fusogenic form of the protein. When considered together, the structural and thermodynamic features of the four domains suggest a possible mechanism whereby the HR regions, initially sequestered in the native S glycoprotein spike, are released and refold sequentially to promote membrane fusion. Our results provide a structural framework for understanding the control of membrane fusion and should guide efforts to intervene in the SARS coronavirus entry process.
GO:0046789
host cell surface receptor binding
GO:0039654
fusion of virus membrane with host endosome membrane
GO:0046813
receptor-mediated virion attachment to host cell
GO:0009405
pathogenesis
GO:0019031
viral envelope
GO:0055036
virion membrane
GO:0020002
host cell plasma membrane
GO:0044173
host cell endoplasmic reticulum-Golgi intermediate compartment membrane
GO:0016021
integral component of membrane
Chains G, H, I, J, K and L were removed as chains A, B, C, D, E and F represent the biologically relevant hexamer.
6
1
Coils and zippers
Coiled coil (tetrameric)
A
Spike glycoprotein
Human SARS coronavirus
NQKQIANQFNKAISQIQESLTTTSTALGKLQDVVNQNAQALNTLVKQLSS
50
P59594
901
950
4%
UniRef90_P59594
901
950
secondary structure
helix
902
948
pfam
PF01601.13
Corona_S2
648
1252
B
Spike glycoprotein
Human SARS coronavirus
DISGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL
36
P59594
1150
1185
2.9%
UniRef90_P59594
1150
1185
secondary structure
helix
1162
1178
pfam
PF01601.13
Corona_S2
648
1252
C
Spike glycoprotein
Human SARS coronavirus
NQKQIANQFNKAISQIQESLTTTSTALGKLQDVVNQNAQALNTLVKQLSS
50
P59594
901
950
4%
UniRef90_P59594
901
950
secondary structure
helix
903
946
pfam
PF01601.13
Corona_S2
648
1252
D
Spike glycoprotein
Human SARS coronavirus
DISGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL
36
P59594
1150
1185
2.9%
UniRef90_P59594
1150
1185
secondary structure
helix
1162
1178
pfam
PF01601.13
Corona_S2
648
1252
E
Spike glycoprotein
Human SARS coronavirus
NQKQIANQFNKAISQIQESLTTTSTALGKLQDVVNQNAQALNTLVKQLSS
50
P59594
901
950
4%
UniRef90_P59594
901
950
secondary structure
helix
902
948
pfam
PF01601.13
Corona_S2
648
1252
F
Spike glycoprotein
Human SARS coronavirus
DISGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL
36
P59594
1150
1185
2.9%
UniRef90_P59594
1150
1185
secondary structure
helix
1162
1178
pfam
PF01601.13
Corona_S2
648
1252
The subunits in the structure are bound via coiled coil interactions (PMID:16698550). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
2beq
2bez
MF2120032
BenM DNA binding domain dimer
3m1e
X-ray
1.80
homodimer
Acinetobacter baylyi
Alanazi, A., Neidle, E.L., Momany, C.
Crystal structure of the unbound LysR-type transcriptional regulator BenM DNA binding domain
Acta Crystallogr. D Biol. Crystallogr.
2013
-
GO:0003700
transcription factor activity, sequence-specific DNA binding
GO:0003677
DNA binding
GO:0006351
transcription, DNA-templated
GO:0019439
aromatic compound catabolic process
GO:0006355
regulation of transcription, DNA-templated
Chain B was generated from chain A using the biomatrices described in the original PDB file.
2
1
Other
Other
A
HTH-type transcriptional regulator BenM
Acinetobacter baylyi
MELRHLRYFVAVVEEQSFTKAADKLCIAQPPLSRQIQNLEEELGIQLLERGSRPVKTTPEGHFFYQYAIKLLSNVDQMVSMTKRIASGHHHHHH
94
O68014
1
94
30.9%
UniRef90_O68014
1
87
secondary structure
helix
3
15
secondary structure
helix
18
24
secondary structure
helix
29
43
secondary structure
beta
48
48
secondary structure
beta
57
57
secondary structure
helix
59
86
pfam
PF00126.24
HTH_1
3
62
B
HTH-type transcriptional regulator BenM
Acinetobacter baylyi
MELRHLRYFVAVVEEQSFTKAADKLCIAQPPLSRQIQNLEEELGIQLLERGSRPVKTTPEGHFFYQYAIKLLSNVDQMVSMTKRIASGHHHHHH
94
O68014
1
94
30.9%
UniRef90_O68014
1
87
secondary structure
helix
3
15
secondary structure
helix
18
24
secondary structure
helix
29
43
secondary structure
beta
48
48
secondary structure
beta
57
57
secondary structure
helix
59
86
pfam
PF00126.24
HTH_1
3
62
A
The N-terminal dimerization regions of BenM is highly mobile evading structure determination by X-ray (PMID:19400783).
B
The N-terminal dimerization regions of BenM is highly mobile evading structure determination by X-ray (PMID:19400783).
4ihs
4iht
3k1m
3k1n
3k1p
MF2210015
H2A-H2B histone dimer (S. cerevisiae), containing histone variants H2A.2 and H2B.1
4kud
X-ray
3.20
heterodimer
Saccharomyces cerevisiae
23934152
Yang D, Fang Q, Wang M, Ren R, Wang H, He M, Sun Y, Yang N, Xu RM
Nα-acetylated Sir3 stabilizes the conformation of a nucleosome-binding loop in the BAH domain.
Nat. Struct. Mol. Biol.
2013
In Saccharomyces cerevisiae, acetylation of the Sir3 N terminus is important for transcriptional silencing. This covalent modification promotes the binding of the Sir3 BAH domain to the nucleosome, but a mechanistic understanding of this phenomenon is lacking. By X-ray crystallography, we show here that the acetylated N terminus of Sir3 does not interact with the nucleosome directly. Instead, it stabilizes a nucleosome-binding loop in the BAH domain.
Chains A, B, E, F, G, H, I, J, K and L have been removed to highlight the basic interaction that forms the histone dimer composed of chains C and D.
2
2
Histone-like interactions
Histones
C
Histone H2A.2
Saccharomyces cerevisiae
MAGGKGGKAGSAAKASQSRSAKAGLTFPVGRVHRLLRRGNYAQRIGSGAPVYLTAVLEYLAAEILELAGNAARDNKKTRIIPRHLQLAIRNDDELNKLLGNVTIAQGGVLPNIHQNLLPKKSAKTAKASQEL
132
P04912
1
132
100%
UniRef90_P04911
1
132
secondary structure
helix
19
22
secondary structure
helix
29
38
secondary structure
beta
44
45
secondary structure
helix
49
73
secondary structure
beta
79
80
secondary structure
helix
82
91
secondary structure
helix
93
98
pfam
PF00125.21
Histone
4
92
pfam
PF16211.2
Histone_H2A_C
93
127
D
Histone H2B.1
Saccharomyces cerevisiae
MSAKAEKKPASKAPAEKKPAAKKTSTSTDGKKRSKARKETYSSYIYKVLKQTHPDTGISQKSMSILNSFVNDIFERIATEASKLAAYNKKSTISAREIQTAVRLILPGELAKHAVSEGTRAVTKYSSSTQA
131
P02293
1
131
100%
UniRef90_P02293
1
131
secondary structure
helix
42
52
secondary structure
beta
57
58
secondary structure
helix
60
87
secondary structure
beta
92
93
secondary structure
helix
95
105
secondary structure
helix
108
128
pfam
PF00125.21
Histone
1
105
Histones form parts of the nucleosome particle by dimerization and subsequent multimerization (PMID:1946434). The dimer contains both histone subunits in a highly intertwined conformation reflecting the possible domain-swapped origins of the structure (PMID:17391511). Accordingly, this dimerization has been experimentally characterized to be coupled to the structure formation of both interacting partners (PMID:12779337); this synergistic folding has been shown separately for H2A-H2B dimers (PMID:15588829) and H3-H4 dimers as well (PMID:15096635). Histones containing various types of monomeric subunits can exhibit varying stability and folding kinetics. E.g. in the case of H3-H4 histones, the dimerization is a complex process with the two monomers first adopting an intermediate state upon encounter and then reaching the classical histone fold through restructurization (PMID:12779337). However, independent of composition and folding kinetics, all histones appear to fold in a cooperative fashion that is coupled to binding (PMID:11669650).
4wnn
5bt1
MF2120033
E. coli proline utilization A (PutA) DNA-binding domain
2ay0
X-ray
2.10
homodimer
Escherichia coli
17001030
Larson JD, Jenkins JL, Schuermann JP, Zhou Y, Becker DF, Tanner JJ
Crystal structures of the DNA-binding domain of Escherichia coli proline utilization A flavoprotein and analysis of the role of Lys9 in DNA recognition.
Protein Sci.
2006
11
15
2630-41
PutA (proline utilization A) from Escherichia coli is a 1320-amino-acid residue protein that is both a bifunctional proline catabolic enzyme and an autogenous transcriptional repressor. Here, we report the first crystal structure of a PutA DNA-binding domain along with functional analysis of a mutant PutA defective in DNA binding. Crystals were grown using a polypeptide corresponding to residues 1-52 of E. coli PutA (PutA52). The 2.1 Angstrom resolution structure of PutA52 mutant Lys9Met was determined using Se-Met MAD phasing, and the structure of native PutA52 was solved at 1.9 Angstrom resolution using molecular replacement. Residues 3-46 form a ribbon-helix-helix (RHH) substructure, thus establishing PutA as the largest protein to contain an RHH domain. The PutA RHH domain forms the intertwined dimer with tightly packed hydrophobic core that is characteristic of the RHH family. The structures were used to examine the three-dimensional context of residues conserved in PutA RHH domains. Homology modeling suggests that Lys9 and Thr5 contact DNA bases through the major groove, while Arg15, Thr28, and His30 may interact with the phosphate backbone. Lys9 is shown to be essential for specific recognition of put control DNA using gel shift analysis of the Lys9Met mutant of full-length PutA. Lys9 is disordered in the PutA52 structure, which implies an induced-fit binding mechanism in which the side chain of Lys9 becomes ordered through interaction with DNA. These results provide new insights into the structural basis of DNA recognition by PutA and reveal three-dimensional structural details of the PutA dimer interface.
GO:0004657
proline dehydrogenase activity
GO:0000986
bacterial-type RNA polymerase core promoter proximal region sequence-specific DNA binding
GO:0050660
flavin adenine dinucleotide binding
GO:0003842
1-pyrroline-5-carboxylate dehydrogenase activity
GO:0004029
aldehyde dehydrogenase (NAD) activity
GO:0001141
transcriptional repressor activity, bacterial-type RNA polymerase core promoter proximal region sequence-specific binding
GO:0010133
proline catabolic process to glutamate
GO:0006561
proline biosynthetic process
GO:0055114
oxidation-reduction process
GO:0045892
negative regulation of transcription, DNA-templated
GO:0006351
transcription, DNA-templated
GO:0009898
cytoplasmic side of plasma membrane
Chains C, D, E and F were removed as chains A and B represent the biologically relevant dimer.
2
1
Other
Ribbon-helix-helix (RHH)
A
Bifunctional protein PutA
Escherichia coli
MGTTTMGVMLDDATRERIKSAATRIDRTPHWLIKQAIFSYLEQLENSDTLPEHHHHHH
58
P09546
1
52
3.9%
UniRef90_P09546
1
52
secondary structure
beta
4
10
secondary structure
helix
12
24
secondary structure
helix
29
43
B
Bifunctional protein PutA
Escherichia coli
MGTTTMGVMLDDATRERIKSAATRIDRTPHWLIKQAIFSYLEQLENSDTLPEHHHHHH
58
P09546
1
52
3.9%
UniRef90_P09546
1
52
secondary structure
beta
4
10
secondary structure
helix
12
23
secondary structure
helix
29
43
The interacting chains form a ribbon-helix-helix (RHH) structure (PMID:17001030). These structures in general have been described with the two monomers adopting a stable conformation upon the interaction (PMID:17676053). The hydrophobic core stabilizing the complex is formed by both interactors and is thus absent prior to the interaction (PMID:25713077).
2gpe
2rbf
MF4140005
SARS-Coronavirus HR2 Domain (post-fusion, tetrameric form)
1zv7
X-ray
1.70
homotetramer
Human SARS coronavirus
16698550
Deng Y, Liu J, Zheng Q, Yong W, Lu M
Structures and polymorphic interactions of two heptad-repeat regions of the SARS virus S2 protein.
Structure
2006
5
14
889-99
Entry of SARS coronavirus into its target cell requires large-scale structural transitions in the viral spike (S) glycoprotein in order to induce fusion of the virus and cell membranes. Here we describe the identification and crystal structures of four distinct alpha-helical domains derived from the highly conserved heptad-repeat (HR) regions of the S2 fusion subunit. The four domains are an antiparallel four-stranded coiled coil, a parallel trimeric coiled coil, a four-helix bundle, and a six-helix bundle that is likely the final fusogenic form of the protein. When considered together, the structural and thermodynamic features of the four domains suggest a possible mechanism whereby the HR regions, initially sequestered in the native S glycoprotein spike, are released and refold sequentially to promote membrane fusion. Our results provide a structural framework for understanding the control of membrane fusion and should guide efforts to intervene in the SARS coronavirus entry process.
GO:0046789
host cell surface receptor binding
GO:0046813
receptor-mediated virion attachment to host cell
GO:0039654
fusion of virus membrane with host endosome membrane
GO:0009405
pathogenesis
GO:0044173
host cell endoplasmic reticulum-Golgi intermediate compartment membrane
GO:0019031
viral envelope
GO:0020002
host cell plasma membrane
GO:0055036
virion membrane
GO:0016021
integral component of membrane
Chains C and D were generated from chains A and B, respectively, using the biomatrices described in the original PDB file.
4
1
Coils and zippers
Coiled coil (tetrameric)
A
Spike glycoprotein
Human SARS coronavirus
DISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIK
44
P59594
1150
1193
3.5%
UniRef90_P59594
1150
1193
secondary structure
helix
1151
1186
pfam
PF01601.13
Corona_S2
648
1252
B
Spike glycoprotein
Human SARS coronavirus
DISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIK
44
P59594
1150
1193
3.5%
UniRef90_P59594
1150
1193
secondary structure
helix
1154
1184
pfam
PF01601.13
Corona_S2
648
1252
C
Spike glycoprotein
Human SARS coronavirus
DISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIK
44
P59594
1150
1193
3.5%
UniRef90_P59594
1150
1193
secondary structure
helix
1151
1186
pfam
PF01601.13
Corona_S2
648
1252
D
Spike glycoprotein
Human SARS coronavirus
DISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIK
44
P59594
1150
1193
3.5%
UniRef90_P59594
1150
1193
secondary structure
helix
1154
1184
pfam
PF01601.13
Corona_S2
648
1252
The subunits in the structure are bound via coiled coil interactions (PMID:16698550). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
MF2200015
H2A-H2B histone dimer (human), containing histone variants H2A type 1-A and H2B type 1-J
5gt0
X-ray
2.82
heterodimer
Homo sapiens
27992841
Padavattan S, Thiruselvam V, Shinagawa T, Hasegawa K, Kumasaka T, Ishii S, Kumarevel T
Structural analyses of the nucleosome complexes with human testis-specific histone variants, hTh2a and hTh2b.
Biophys. Chem.
2017
221
41-48
Th2a and Th2b are the testis-specific histone variants highly expressed during spermatogenesis. Approximately 4% of the genome is retained in nucleosomes in mature human sperm, which is enriched at loci of developmental importance. Our recent studies revealed that the mouse histone variant homologs TH2a and TH2b are involved in reprogramming. In the present work, we report three nucleosome structures (NCPs) with human testis-specific histone variants hTh2a and hTh2b, [hGcH (hTh2a-hTh2b-H3-H4), hGcHV1 (hTh2a-H2b-H3-H4) and hGcHV2 (H2a-hTh2b-H3-H4)] and a 146-base pair (bp) duplex DNA fragment at ~3.0Å resolutions. These crystal structures revealed two major changes within the nucleosomes, either with hTh2a, hTh2b or both variants, as compared to the canonical counterpart. First, the H-bonding interactions between the L1-L1' interfaces mediated by the hTh2a/hTh2a' L1-loops are lost. Second, the histone dimer-DNA contacts are considerably reduced, and these changes are localized around ±31 to 35-bp from the nucleosome entry/exit sites. Thus, the modified functional residues at the N- and C-terminal ends of histone variants are responsible for the observed structural changes and regulate the gene expression through specific structural alterations in the chromatin by modulating the chromatin-associated binding proteins.
Chains A, B, E, F, G, H, I and J have been removed to highlight the basic interaction that forms the histone dimer composed of chains C and D.
2
2
Histone-like interactions
Histones
C
Histone H2A type 1-A
Homo sapiens
SGRGKQGGKARAKSKSRSSRAGLQFPVGRIHRLLRKGNYAERIGAGAPVYLAAVLEYLTAEILELAGNASRDNKKTRIIPRHLQLAIRNDEELNKLLGGVTIAQGGVLPNIQAVLLPKKTESHHHKAQSK
130
Q96QV6
2
131
99.2%
UniRef90_P04908
2
131
secondary structure
helix
20
22
secondary structure
helix
28
36
secondary structure
beta
43
44
secondary structure
helix
47
73
secondary structure
beta
78
79
secondary structure
helix
81
90
secondary structure
helix
92
97
secondary structure
helix
114
116
pfam
PF00125.21
Histone
2
91
pfam
PF16211.2
Histone_H2A_C
92
126
D
Histone H2B type 1-C/E/F/G/I
Homo sapiens
PEPAKSAPAPKKGSKKAVTKAQKKDGKKRKRSRKESYSVYVYKVLKQVHPDTGISSKAMGIMNSFVNDIFERIAGEASRLAHYNKRSTITSREIQTAVRLLLPGELAKHAVSEGTKAVTKYTSSK
125
P62807
2
126
99.2%
UniRef90_P62807
2
126
secondary structure
helix
39
49
secondary structure
beta
54
55
secondary structure
helix
57
84
secondary structure
beta
89
90
secondary structure
helix
92
102
secondary structure
helix
105
124
pfam
PF00125.21
Histone
2
102
Histones form parts of the nucleosome particle by dimerization and subsequent multimerization (PMID:1946434). The dimer contains both histone subunits in a highly intertwined conformation reflecting the possible domain-swapped origins of the structure (PMID:17391511). Accordingly, this dimerization has been experimentally characterized to be coupled to the structure formation of both interacting partners (PMID:12779337); this synergistic folding has been shown separately for H2A-H2B dimers (PMID:15588829) and H3-H4 dimers as well (PMID:15096635). Histones containing various types of monomeric subunits can exhibit varying stability and folding kinetics. E.g. in the case of H3-H4 histones, the dimerization is a complex process with the two monomers first adopting an intermediate state upon encounter and then reaching the classical histone fold through restructurization (PMID:12779337). However, independent of composition and folding kinetics, all histones appear to fold in a cooperative fashion that is coupled to binding (PMID:11669650).
MF2200016
H2A-H2B histone dimer (human), containing histone variants H2A type 1-D and H2B type 1-A
5gt3
X-ray
2.91
heterodimer
Homo sapiens
27992841
Padavattan S, Thiruselvam V, Shinagawa T, Hasegawa K, Kumasaka T, Ishii S, Kumarevel T
Structural analyses of the nucleosome complexes with human testis-specific histone variants, hTh2a and hTh2b.
Biophys. Chem.
2017
221
41-48
Th2a and Th2b are the testis-specific histone variants highly expressed during spermatogenesis. Approximately 4% of the genome is retained in nucleosomes in mature human sperm, which is enriched at loci of developmental importance. Our recent studies revealed that the mouse histone variant homologs TH2a and TH2b are involved in reprogramming. In the present work, we report three nucleosome structures (NCPs) with human testis-specific histone variants hTh2a and hTh2b, [hGcH (hTh2a-hTh2b-H3-H4), hGcHV1 (hTh2a-H2b-H3-H4) and hGcHV2 (H2a-hTh2b-H3-H4)] and a 146-base pair (bp) duplex DNA fragment at ~3.0Å resolutions. These crystal structures revealed two major changes within the nucleosomes, either with hTh2a, hTh2b or both variants, as compared to the canonical counterpart. First, the H-bonding interactions between the L1-L1' interfaces mediated by the hTh2a/hTh2a' L1-loops are lost. Second, the histone dimer-DNA contacts are considerably reduced, and these changes are localized around ±31 to 35-bp from the nucleosome entry/exit sites. Thus, the modified functional residues at the N- and C-terminal ends of histone variants are responsible for the observed structural changes and regulate the gene expression through specific structural alterations in the chromatin by modulating the chromatin-associated binding proteins.
Chains A, B, E, F, G, H, I and J have been removed to highlight the basic interaction that forms the histone dimer composed of chains C and D.
2
2
Histone-like interactions
Histones
C
Histone H2A type 1-D
Homo sapiens
SGRGKQGGKARAKAKTRSSRAGLQFPVGRVHRLLRKGNYSERVGAGAPVYLAAVLEYLTAEILELAGNAARDNKKTRIIPRHLQLAIRNDEELNKLLGKVTIAQGGVLPNIQAVLLPKKTESHHKAKGK
129
P20671
2
130
99.2%
UniRef90_P20671
2
130
secondary structure
helix
18
22
secondary structure
helix
28
36
secondary structure
beta
43
44
secondary structure
helix
47
73
secondary structure
beta
78
79
secondary structure
helix
81
90
secondary structure
helix
92
97
secondary structure
helix
114
116
pfam
PF00125.21
Histone
2
91
pfam
PF16211.2
Histone_H2A_C
92
126
D
Histone H2B type 1-A
Homo sapiens
PEVSSKGATISKKGFKKAVVKTQKKEGKKRKRTRKESYSIYIYKVLKQVHPDTGISSKAMSIMNSFVTDIFERIASEASRLAHYSKRSTISSREIQTAVRLLLPGELAKHAVSEGTKAVTKYTSSK
126
Q96A08
2
127
99.2%
UniRef90_P70696
2
127
secondary structure
helix
40
50
secondary structure
beta
55
56
secondary structure
helix
58
85
secondary structure
beta
90
91
secondary structure
helix
93
103
secondary structure
helix
106
124
pfam
PF00125.21
Histone
2
103
Histones form parts of the nucleosome particle by dimerization and subsequent multimerization (PMID:1946434). The dimer contains both histone subunits in a highly intertwined conformation reflecting the possible domain-swapped origins of the structure (PMID:17391511). Accordingly, this dimerization has been experimentally characterized to be coupled to the structure formation of both interacting partners (PMID:12779337); this synergistic folding has been shown separately for H2A-H2B dimers (PMID:15588829) and H3-H4 dimers as well (PMID:15096635). Histones containing various types of monomeric subunits can exhibit varying stability and folding kinetics. E.g. in the case of H3-H4 histones, the dimerization is a complex process with the two monomers first adopting an intermediate state upon encounter and then reaching the classical histone fold through restructurization (PMID:12779337). However, independent of composition and folding kinetics, all histones appear to fold in a cooperative fashion that is coupled to binding (PMID:11669650).
MF2200017
H3-H4 histone dimer (human), containing histone variant H3.3C
4z5t
X-ray
2.80
heterodimer
Homo sapiens
26779285
Urahama T, Harada A, Maehara K, Horikoshi N, Sato K, Sato Y, Shiraishi K, Sugino N, Osakabe A, Tachiwana H, Kagawa W, Kimura H, Ohkawa Y, Kurumizaka H
Histone H3.5 forms an unstable nucleosome and accumulates around transcription start sites in human testis.
Epigenetics Chromatin
2016
9
2
CONCLUSIONS: We performed comprehensive studies of H3.5, and found the instability of the H3.5 nucleosome and the accumulation of H3.5 protein around TSSs in human testis. The unstable H3.5 nucleosome may function in the chromatin dynamics around the TSSs, during spermatogenesis. RESULTS: We found that the H3.5 nucleosome is less stable than the H3.3 nucleosome. The crystal structure of the H3.5 nucleosome showed that the H3.5-specific Leu103 residue, which corresponds to the H3.3 Phe104 residue, reduces the hydrophobic interaction with histone H4. Mutational analyses revealed that the H3.5-specific Leu103 residue is responsible for the instability of the H3.5 nucleosome, both in vitro and in living cells. The H3.5 protein was present in human seminiferous tubules, but little to none was found in mature sperm. A chromatin immunoprecipitation coupled with sequencing analysis revealed that H3.5 accumulated around transcription start sites (TSSs) in testicular cells. BACKGROUND: Human histone H3.5 is a non-allelic H3 variant evolutionally derived from H3.3. The H3.5 mRNA is highly expressed in human testis. However, the function of H3.5 has remained poorly understood.
Chains C, D, E, F, G, H, I and J have been removed to highlight the basic interaction that forms the histone dimer composed of chains A and B.
2
2
Histone-like interactions
Histones
A
Histone H3.3C
Homo sapiens
GSHMARTKQTARKSTGGKAPRKQLATKAARKSTPSTCGVKPHRYRPGTVALREIRRYQKSTELLIRKLPFQRLVREIAQDFNTDLRFQSAAVGALQEASEAYLVGLLEDTNLCAIHAKRVTIMPKDIQLARRIRGERA
138
Q6NXT2
1
135
100%
UniRef90_Q6NXT2
1
135
secondary structure
helix
45
56
secondary structure
helix
64
78
secondary structure
beta
83
84
secondary structure
helix
86
113
secondary structure
beta
118
119
secondary structure
helix
121
131
pfam
PF00125.21
Histone
1
131
B
Histone H4
Homo sapiens
GSHMSGRGKGGKGLGKGGAKRHRKVLRDNIQGITKPAIRRLARRGGVKRISGLIYEETRGVLKVFLENVIRDAVTYTEHAKRKTVTAMDVVYALKRQGRTLYGFGG
106
P62805
1
103
100%
UniRef90_P62805
1
103
secondary structure
helix
26
29
secondary structure
helix
32
41
secondary structure
beta
46
47
secondary structure
helix
51
76
secondary structure
beta
81
82
secondary structure
helix
84
93
pfam
PF15511.3
CENP-T_C
18
99
Histones form parts of the nucleosome particle by dimerization and subsequent multimerization (PMID:1946434). The dimer contains both histone subunits in a highly intertwined conformation reflecting the possible domain-swapped origins of the structure (PMID:17391511). Accordingly, this dimerization has been experimentally characterized to be coupled to the structure formation of both interacting partners (PMID:12779337); this synergistic folding has been shown separately for H2A-H2B dimers (PMID:15588829) and H3-H4 dimers as well (PMID:15096635). Histones containing various types of monomeric subunits can exhibit varying stability and folding kinetics. E.g. in the case of H3-H4 histones, the dimerization is a complex process with the two monomers first adopting an intermediate state upon encounter and then reaching the classical histone fold through restructurization (PMID:12779337). However, independent of composition and folding kinetics, all histones appear to fold in a cooperative fashion that is coupled to binding (PMID:11669650).
MF2120034
Bacillus subtilis antitoxin MazE
4me7
X-ray
2.92
homodimer
Bacillus subtilis
24120662
Simanshu DK, Yamaguchi Y, Park JH, Inouye M, Patel DJ
Structural Basis of mRNA Recognition and Cleavage by Toxin MazF and Its Regulation by Antitoxin MazE in Bacillus subtilis.
Mol. Cell
2013
MazF is an mRNA interferase, which, upon activation during stress conditions, cleaves mRNAs in a sequence-specific manner, resulting in cellular growth arrest. During normal growth conditions, the MazF toxin is inactivated through binding to its cognate antitoxin, MazE. How MazF specifically recognizes its mRNA target and carries out cleavage and how the formation of the MazE-MazF complex inactivates MazF remain unclear. We present crystal structures of MazF in complex with mRNA substrate and antitoxin MazE in Bacillus subtilis. The structure of MazF in complex with uncleavable UUdUACAUAA RNA substrate defines the molecular basis underlying the sequence-specific recognition of UACAU and the role of residues involved in the cleavage through site-specific mutational studies. The structure of the heterohexameric (MazF)2-(MazE)2-(MazF)2 complex in Bacillus subtilis, supplemented by mutational data, demonstrates that the positioning of the C-terminal helical segment of MazE within the RNA-binding channel of the MazF dimer prevents mRNA binding and cleavage by MazF.
GO:0042802
identical protein binding
GO:0006355
regulation of transcription, DNA-templated
Chains A, B, C and D were removed and chains E and F were truncated to include residues 6-52 and 7-52, respectively, to highlight the dimeric interaction.
2
1
Other
Ribbon-helix-helix (RHH)
E
Antitoxin EndoAI
Bacillus subtilis
SMSESSARTEMKISLPENLVAELDGVAMREKRSRNELISQAVRAYVSERTTRHNRDLMRRGYMEMAKINLNISSEAHFAECEAETTVERLVSGG
94
P96621
1
93
100%
UniRef90_P96621
1
93
secondary structure
beta
11
14
secondary structure
helix
17
26
secondary structure
helix
28
31
secondary structure
helix
35
52
pfam
PF01402.18
RHH_1
11
47
F
Antitoxin EndoAI
Bacillus subtilis
SMSESSARTEMKISLPENLVAELDGVAMREKRSRNELISQAVRAYVSERTTRHNRDLMRRGYMEMAKINLNISSEAHFAECEAETTVERLVSGG
94
P96621
1
93
100%
UniRef90_P96621
1
93
secondary structure
beta
9
13
secondary structure
helix
17
26
secondary structure
helix
28
31
secondary structure
helix
35
52
pfam
PF01402.18
RHH_1
11
47
The interacting chains form a ribbon-helix-helix (RHH) structure (PMID:17007877). These structures in general have been described with the two monomers adopting a stable conformation upon the interaction (PMID:17676053). The hydrophobic core stabilizing the complex is formed by both interactors and is thus absent prior to the interaction (PMID:25713077).
MF2100018
Dimeric cytoplasmic domain of syndecan-4
1ejp
NMR
homodimer
Homo sapiens
11456484
Shin J, Lee W, Lee D, Koo BK, Han I, Lim Y, Woods A, Couchman JR, Oh ES
Solution structure of the dimeric cytoplasmic domain of syndecan-4.
Biochemistry
2001
29
40
8471-8
The syndecans, transmembrane proteoglycans which are involved in the organization of cytoskeleton and/or actin microfilaments, have important roles as cell surface receptors during cell-cell and/or cell-matrix interactions. Since previous studies indicate that the function of the syndecan-4 cytoplasmic domain is dependent on its oligomeric status, the conformation of the syndecan-4 cytoplasmic domain itself is important in the understanding of its biological roles. Gel filtration results show that the syndecan-4 cytoplasmic domain (4L) itself forms a dimer stabilized by ionic interactions between peptides at physiological pH. Commensurately, the NMR structures demonstrate that syndecan-4L is a compact intertwined dimer with a symmetric clamp shape in the central variable V region with a root-mean-square deviation between backbone atom coordinates of 0.95 A for residues Leu(186)-Ala(195). The molecular surface of the 4L dimer is highly positively charged. In addition, no intersubunit NOEs in membrane proximal amino acid resides (C1 region) have been observed, demonstrating that the C1 region is mostly unstructured in the syndecan-4L dimer. Interestingly, two parallel strands of 4L form a cavity in the center of the dimeric twist similar to our previously reported 4V structure. The overall topology of the central variable region within the 4L structure is very similar to that of 4V complexed with the phosphatidylinositol 4,5-bisphosphate; however, the intersubunit interaction mode is affected by the presence of C1 and C2 regions. Therefore, we propose that although the 4V region in the full cytoplasmic domain has a tendency for strong peptide--peptide interaction, it may not be enough to overcome the repulsion of the C1 regions of syndecan-4L.
GO:0070053
thrombospondin receptor activity
GO:0001968
fibronectin binding
GO:0005080
protein kinase C binding
GO:0051496
positive regulation of stress fiber assembly
GO:1903543
positive regulation of exosomal secretion
GO:0042060
wound healing
GO:0051894
positive regulation of focal adhesion assembly
GO:0045860
positive regulation of protein kinase activity
GO:0016477
cell migration
GO:0001523
retinoid metabolic process
GO:0001843
neural tube closure
GO:1903553
positive regulation of extracellular exosome assembly
GO:0006024
glycosaminoglycan biosynthetic process
GO:0060122
inner ear receptor stereocilium organization
GO:0010762
regulation of fibroblast migration
GO:0007165
signal transduction
GO:0001657
ureteric bud development
GO:0006027
glycosaminoglycan catabolic process
GO:0005887
integral component of plasma membrane
GO:0070062
extracellular exosome
GO:0045121
membrane raft
GO:0005796
Golgi lumen
GO:0005925
focal adhesion
GO:0043034
costamere
GO:0009986
cell surface
GO:0043202
lysosomal lumen
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
1
Other
Other
A
Syndecan-4
Homo sapiens
RMKKKDEGSYDLGKKPIYKKAPTNEFYA
28
P31431
171
198
14.1%
UniRef90_P31431
171
198
pfam
PF01034.17
Syndecan
139
196
B
Syndecan-4
Homo sapiens
RMKKKDEGSYDLGKKPIYKKAPTNEFYA
28
P31431
171
198
14.1%
UniRef90_P31431
171
198
pfam
PF01034.17
Syndecan
139
196
A
The cytoplasmic domain of Syndecan-4 has been shown to adopt a stable structure upon binding to a partner protein (either through binding to an ordered domain PMID:16533050 or through dimerization PMID:11456484).
B
The cytoplasmic domain of Syndecan-4 has been shown to adopt a stable structure upon binding to a partner protein (either through binding to an ordered domain PMID:16533050 or through dimerization PMID:11456484).
1ejq
MF2211003
Yeast elongin C in complex with a von Hippel-Lindau peptide
1hv2
NMR
heterodimer
Saccharomyces cerevisiae / Mus musculus
11545595
Botuyan MV, Mer G, Yi GS, Koth CM, Case DA, Edwards AM, Chazin WJ, Arrowsmith CH
Solution structure and dynamics of yeast elongin C in complex with a von Hippel-Lindau peptide.
J. Mol. Biol.
2001
1
312
177-86
Elongin is a transcription elongation factor that stimulates the rate of elongation by suppressing transient pausing by RNA polymerase II at many sites along the DNA. It is heterotrimeric in mammals, consisting of elongins A, B and C subunits, and bears overall similarity to a class of E3 ubiquitin ligases known as SCF (Skp1-Cdc53 (cullin)-F-box) complexes. A subcomplex of elongins B and C is a target for negative regulation by the von Hippel-Lindau (VHL) tumor-suppressor protein. Elongin C from Saccharomyces cerevisiae, Elc1, exhibits high sequence similarity to mammalian elongin C. Using NMR spectroscopy we have determined the three-dimensional structure of Elc1 in complex with a human VHL peptide, VHL(157-171), representing the major Elc1 binding site. The bound VHL peptide is entirely helical. Elc1 utilizes two C-terminal helices and an intervening loop to form a binding groove that fits VHL(157-171). Chemical shift perturbation and dynamics analyses reveal that a global conformational change accompanies Elc1/VHL(157-171) complex formation. Moreover, the disappearance of conformational exchange phenomena on the microsecond to millisecond time scale within Elc1 upon VHL peptide binding suggests a role for slow internal motions in ligand recognition.
GO:0005515
protein binding
GO:0005737
cytoplasm
GO:0005634
nucleus
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
2
Other
Other
A
Elongin-C
Saccharomyces cerevisiae
MSQDFVTLVSKDDKEYEISRSAAMISPTLKAMIEGPFRESKGRIELKQFDSHILEKAVEYLNYNLKYSGVSEDDDEIPEFEIPTEMSLELLLAADYLSI
99
Q03071
1
99
100%
UniRef90_Q03071
1
99
secondary structure
beta
5
10
secondary structure
beta
14
19
secondary structure
helix
20
23
secondary structure
helix
27
34
secondary structure
beta
43
46
secondary structure
helix
51
70
secondary structure
helix
84
97
pfam
PF03931.12
Skp1_POZ
4
66
B
Von Hippel-Lindau disease tumor suppressor
Mus musculus
TLKERCLQVVRSLVK
15
P40338
123
137
8.3%
UniRef90_P40338
123
137
secondary structure
helix
124
136
pfam
PF01847.13
VHL
27
172
Both elongin C and the interacting region of VHL are dynamically unstable in isolation and only adopt a stable conformation upon interaction (PMID:11545595).
MF2200018
T-cell surface glycoprotein CD4 and proto-oncogene tyrosine-protein kinase LCK fragments
1q68
NMR
heterodimer
Homo sapiens
14500983
Kim PW, Sun ZY, Blacklow SC, Wagner G, Eck MJ
A zinc clasp structure tethers Lck to T cell coreceptors CD4 and CD8.
Science
2003
5640
301
1725-8
The T cell coreceptors CD4 and CD8 both associate via their cytoplasmic tails with the N-terminus of the Src-family tyrosine kinase Lck. These interactions require zinc and are critical for T cell development and activation. We examined the folding and solution structures of ternary CD4-Lck-Zn2+ and CD8alpha-Lck-Zn2+ complexes. The coreceptor tails and the Lck N-terminus are unstructured in isolation but assemble in the presence of zinc to form compactly folded heterodimeric domains. The cofolded complexes have similar "zinc clasp" cores that are augmented by distinct structural elements. A dileucine motif required for clathrin-mediated endocytosis of CD4 is masked by Lck.
GO:0001948
glycoprotein binding
GO:0019901
protein kinase binding
GO:0030217
T cell differentiation
GO:0050852
T cell receptor signaling pathway
GO:0031295
T cell costimulation
GO:0050690
regulation of defense response to virus by virus
GO:0016032
viral process
GO:0007169
transmembrane receptor protein tyrosine kinase signaling pathway
GO:0045121
membrane raft
GO:0005886
plasma membrane
No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
2
2
Other
Other
A
T-cell surface glycoprotein CD4
Homo sapiens
RCRHRRRQAERLSQIKRLLSEKKTCQCPHRFQKTCSPI
38
P01730
421
458
8.3%
UniRef90_P01730
421
458
secondary structure
helix
431
440
pfam
PF12104.5
Tcell_CD4_C
426
453
B
Tyrosine-protein kinase Lck
Homo sapiens
SHPEDDWLENIDVCENCHYPIVPLDGKGT
29
P06239
7
35
5.7%
UniRef90_P06239
7
35
secondary structure
helix
12
15
The interacting regions of CD4 and Lck were shown using NMR to undergo cooperative folding as a result of the binding (PMID:14500983).