Database accession: MF2211002
Name: c-Myc-Max heterodimeric leucine zipper
PDB ID: 1a93
Experimental method: NMR
Source organism: Pan paniscus / Mus musculus
Primer publication of the structure:
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.
(1998) J. Mol. Biol. 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.
regulation of transcription, DNA-templated Any process that modulates the frequency, rate or extent of cellular DNA-templated transcription.
transcription, DNA-templated The cellular synthesis of RNA on a template of DNA.
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: Myc proto-oncogene protein
Source organism: Pan paniscus
Length: 29 residues
Sequence:Sequence according to PDB SEQRESVQAEEQKLISEEDLLRKRREQLKHKLEQL
UniProtKB AC: A1YG22 (positions: 406-434)Coverage: 6.6%
UniRef90 AC: UniRef90_P01106 (positions: 406-434)
Name: Protein max
Source organism: Mus musculus
Length: 29 residues
Sequence:Sequence according to PDB SEQRESMRRKNDTHQQDIDDLKRQNALLEQQVRAL
UniProtKB AC: P28574 (positions: 74-102)Coverage: 18.1%
UniRef90 AC: UniRef90_P61244 (positions: 74-102)
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.
The 406-434 region described in DisProt entry DP00260 covers 100% of a close homologue of the sequence present in the structure.
The 1-110 region described in DisProt entry DP00084 covers 100% of a close homologue of the sequence present in the structure.