Solution structure of the MEF2A-DNA complex: structural basis for the modulation of DNA bending and specificity by MADS-box transcription factors

EMBO J. 2000 Jun 1;19(11):2615-28. doi: 10.1093/emboj/19.11.2615.


The solution structure of the 33 kDa complex between the dimeric DNA-binding core domain of the transcription factor MEF2A (residues 1-85) and a 20mer DNA oligonucleotide comprising the consensus sequence CTA(A/T)(4)TAG has been solved by NMR. The protein comprises two domains: a MADS-box (residues 1-58) and a MEF2S domain (residues 59-73). Recognition and specificity are achieved by interactions between the MADS-box and both the major and minor grooves of the DNA. A number of critical differences in protein-DNA contacts observed in the MEF2A-DNA complex and the DNA complexes of the related MADS-box transcription factors SRF and MCM1 provide a molecular explanation for modulation of sequence specificity and extent of DNA bending ( approximately 15 versus approximately 70 degrees ). The structure of the MEF2S domain is entirely different from that of the equivalent SAM domain in SRF and MCM1, accounting for the absence of cross-reactivity with other proteins that interact with these transcription factors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Cross Reactions
  • DNA / chemistry*
  • DNA / metabolism
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism
  • Dimerization
  • Humans
  • MADS Domain Proteins
  • MEF2 Transcription Factors
  • Macromolecular Substances
  • Magnetic Resonance Spectroscopy
  • Minichromosome Maintenance 1 Protein
  • Models, Molecular
  • Molecular Sequence Data
  • Myogenic Regulatory Factors
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism
  • Nucleic Acid Conformation / drug effects
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Regulatory Sequences, Nucleic Acid
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Serum Response Factor
  • Solutions
  • Structure-Activity Relationship
  • Transcription Factors / chemistry*
  • Transcription Factors / classification
  • Transcription Factors / metabolism
  • Transcription Factors / pharmacology


  • DNA-Binding Proteins
  • MADS Domain Proteins
  • MEF2 Transcription Factors
  • MEF2A protein, human
  • Macromolecular Substances
  • Minichromosome Maintenance 1 Protein
  • Myogenic Regulatory Factors
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Serum Response Factor
  • Solutions
  • Transcription Factors
  • DNA

Associated data

  • PDB/1C7U