General Information

Database accession: MF2211002

Name: c-Myc-Max heterodimeric leucine zipper

PDB ID: 1a93 PDB

Experimental method: NMR

Assembly: heterodimer

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

PMID: 9680483 PubMed


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.

Function and Biology Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown.

Molecular function:

DNA binding Any molecular function by which a gene product interacts selectively and non-covalently with DNA (deoxyribonucleic acid). GeneOntology

protein dimerization activity The formation of a protein dimer, a macromolecular structure consists of two noncovalently associated identical or nonidentical subunits. GeneOntology

Biological process:

regulation of transcription, DNA-templated Any process that modulates the frequency, rate or extent of cellular DNA-templated transcription. GeneOntology

transcription, DNA-templated The cellular synthesis of RNA on a template of DNA. GeneOntology

Cellular component:

nucleoplasm That part of the nuclear content other than the chromosomes or the nucleolus. GeneOntology

Structure Summary Structural annotations of the participating protein chains.

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

Chain A

Name: Myc proto-oncogene protein

Source organism: Pan paniscus

Length: 29 residues


UniProtKB AC: A1YG22 (positions: 406-434) UniProt Coverage: 6.6%

UniRef90 AC: UniRef90_P01106 (positions: 406-434) UniRef90

Chain B

Name: Protein max

Source organism: Mus musculus

Length: 29 residues


UniProtKB AC: P28574 (positions: 74-102) UniProt Coverage: 18.1%

UniRef90 AC: UniRef90_P61244 (positions: 74-102) UniRef90

Evidence Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding.

Complex evidence:

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.

Chain A:

The 406-434 region described in DisProt entry DP00260 covers 100% of a close homologue of the sequence present in the structure.

Chain B:

The 1-110 region described in DisProt entry DP00084 covers 100% of a close homologue of the sequence present in the structure.

Related Structure(s) Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap).

There are 2 related structures in the Protein Data Bank:

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