3KOV

Structure of MEF2A bound to DNA reveals a completely folded MADS-box/MEF2 domain that recognizes DNA and recruits transcription co-factors


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.279 
  • R-Value Work: 0.221 
  • R-Value Observed: 0.224 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Structure of the MADS-box/MEF2 Domain of MEF2A Bound to DNA and Its Implication for Myocardin Recruitment.

Wu, Y.Dey, R.Han, A.Jayathilaka, N.Philips, M.Ye, J.Chen, L.

(2010) J Mol Biol 397: 520-533

  • DOI: https://doi.org/10.1016/j.jmb.2010.01.067
  • Primary Citation of Related Structures:  
    3KOV

  • PubMed Abstract: 

    Myocyte enhancer factor 2 (MEF2) regulates specific gene expression in diverse developmental programs and adaptive responses. MEF2 recognizes DNA and interacts with transcription cofactors through a highly conserved N-terminal domain referred to as the MADS-box/MEF2 domain. Here we present the crystal structure of the MADS-box/MEF2 domain of MEF2A bound to DNA. In contrast to previous structural studies showing that the MEF2 domain of MEF2A is partially unstructured, the present study reveals that the MEF2 domain participates with the MADS-box in both dimerization and DNA binding as a single domain. The sequence divergence at and immediately following the C-terminal end of the MEF2 domain may allow different MEF2 dimers to recognize different DNA sequences in the flanking regions. The current structure also suggests that the ligand-binding pocket previously observed in the Cabin1-MEF2B-DNA complex and the HDAC9 (histone deacetylase 9)-MEF2B-DNA complex is not induced by cofactor binding but rather preformed by intrinsic folding. However, the structure of the ligand-binding pocket does undergo subtle but significant conformational changes upon cofactor binding. On the basis of these observations, we generated a homology model of MEF2 bound to a myocardin family protein, MASTR, that acts as a potent coactivator of MEF2-dependent gene expression. The model shows excellent shape and chemical complementarity at the binding interface and is consistent with existing mutagenesis data. The apo structure presented here can also serve as a target for virtual screening and soaking studies of small molecules that can modulate the function of MEF2 as research tools and therapeutic leads.


  • Organizational Affiliation

    Division of Molecular and Computational Biology, Departments of Biological Sciences and Chemistry, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, RRI 204c, 1050 Childs Way, Los Angeles, CA 90089, USA.


Macromolecules

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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Myocyte-specific enhancer factor 2AA,
B,
C [auth I],
D [auth J]
90Homo sapiensMutation(s): 0 
Gene Names: MEF2AMEF2
UniProt & NIH Common Fund Data Resources
Find proteins for Q02078 (Homo sapiens)
Explore Q02078 
Go to UniProtKB:  Q02078
PHAROS:  Q02078
GTEx:  ENSG00000068305 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ02078
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains LengthOrganismImage
DNA (5'-D(*AP*AP*CP*TP*AP*TP*TP*TP*AP*TP*AP*AP*G)-3')E [auth C],
G [auth K]
13N/A
Sequence Annotations
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  • Reference Sequence

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Entity ID: 3
MoleculeChains LengthOrganismImage
DNA (5'-D(*TP*CP*TP*TP*AP*TP*AP*AP*AP*TP*AP*GP*T)-3')F [auth D],
H [auth L]
13N/A
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.279 
  • R-Value Work: 0.221 
  • R-Value Observed: 0.224 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 77.801α = 90
b = 77.96β = 90
c = 106.794γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
PHENIXrefinement
PDB_EXTRACTdata extraction

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-02-16
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-11-01
    Changes: Refinement description
  • Version 1.3: 2018-04-04
    Changes: Data collection
  • Version 1.4: 2024-02-21
    Changes: Data collection, Database references