Database accession: MF2201008
Name: Heterodimer of ATF-4 and C/EBP beta
PDB ID: 1ci6
Experimental method: X-ray (2.60 Å)
Source organism: Homo sapiens / Mus musculus
Primer publication of the structure:
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.
(2001) J. Biol. Chem. 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.
RNA polymerase II core promoter proximal region sequence-specific DNA binding Interacting selectively and non-covalently with a sequence of DNA that is in cis with and relatively close to a core promoter for RNA polymerase II.
transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Interacting selectively and non-covalently with a sequence of DNA that is in cis with and relatively close to a core promoter for RNA polymerase II (RNAP II) in order to activate or increase the frequency, rate or extent of transcription from the RNAP II promoter.
protein heterodimerization activity Interacting selectively and non-covalently with a nonidentical protein to form a heterodimer.
transcription from RNA polymerase II promoter The synthesis of RNA from a DNA template by RNA polymerase II, originating at an RNA polymerase II promoter. Includes transcription of messenger RNA (mRNA) and certain small nuclear RNAs (snRNAs).
positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter as a result of an endoplasmic reticulum stress.
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress A series of molecular signals in which an intracellular signal is conveyed to trigger the apoptotic death of a cell. The pathway is induced in response to a stimulus indicating endoplasmic reticulum (ER) stress, and ends when the execution phase of apoptosis is triggered. ER stress usually results from the accumulation of unfolded or misfolded proteins in the ER lumen.
Entry contents: 2 distinct polypeptide molecules
Chains: A, B
Notes: No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
Number of unique protein segments: 2
Name: Cyclic AMP-dependent transcription factor ATF-4
Source organism: Homo sapiens
Length: 63 residues
Sequence:Sequence according to PDB SEQRESMKKLKKMEQNKTAATRYRQKKRAEQEALTGECKELEKKNEALKERADSLAKEIQYLKDLIEEV
UniProtKB AC: P18848 (positions: 279-341)Coverage: 17.9%
UniRef90 AC: UniRef90_P18848 (positions: 280-341)
Name: CCAAT/enhancer-binding protein beta
Source organism: Mus musculus
Length: 63 residues
Sequence:Sequence according to PDB SEQRESMEYKMRRERNNIAVRKSRDKAKMRNLETQHKVLELTAENERLQKKVEQLSRELSTLRNLFKQL
UniProtKB AC: P28033 (positions: 223-285)Coverage: 21.3%
UniRef90 AC: UniRef90_P28033 (positions: 224-285)
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.
No related structure was found in the Protein Data Bank.