2A93

NMR SOLUTION STRUCTURE OF THE C-MYC-MAX HETERODIMERIC LEUCINE ZIPPER, 40 STRUCTURES


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 40 
  • Conformers Submitted: 40 
  • Selection Criteria: LEAST RESTRAINT VIOLATION ONLY. 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Insights into the mechanism of heterodimerization from the 1H-NMR solution structure of the c-Myc-Max heterodimeric leucine zipper.

Lavigne, P.Crump, M.P.Gagne, S.M.Hodges, R.S.Kay, C.M.Sykes, B.D.

(1998) J Mol Biol 281: 165-181

  • DOI: https://doi.org/10.1006/jmbi.1998.1914
  • Primary Citation of Related Structures:  
    1A93, 2A93

  • PubMed Abstract: 

    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.


  • Organizational Affiliation

    The Protein Engineering Network of Centres of Excellence, Department of Biochemistry, University of Alberta, Edmonton, Alberta, T6G 2S2, Canada.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
C-MYC-MAX HETERODIMERIC LEUCINE ZIPPER34N/AMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P01106 (Homo sapiens)
Explore P01106 
Go to UniProtKB:  P01106
PHAROS:  P01106
GTEx:  ENSG00000136997 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP01106
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
C-MYC-MAX HETERODIMERIC LEUCINE ZIPPER34N/AMutation(s): 0 
UniProt
Find proteins for P28574 (Mus musculus)
Explore P28574 
Go to UniProtKB:  P28574
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP28574
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 40 
  • Conformers Submitted: 40 
  • Selection Criteria: LEAST RESTRAINT VIOLATION ONLY. 

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1999-01-27
    Type: Initial release
  • Version 1.1: 2008-03-24
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2022-03-09
    Changes: Database references, Derived calculations, Experimental preparation, Other