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

The solution structure of the 33 kDa complex between the dimeric DNA-blindi ng core domain of the transcription factor MEF2A (residues 1-85) and a 20me r 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 contac ts observed in the MEF2A-DNA complex and the DNA complexes of the related M ADS-box transcription factors SRF and MCM1 provide a molecular explanation for modulation of sequence specificity and extent of DNA bending (similar t o 15 versus similar to 70 degrees), The structure of the MEF2S domain is en tirely different from that of the equivalent SAM domain in SRF and MCM1, ac counting for the absence of cross-reactivity with other proteins that inter act with these transcription factors.