Structure of the MADS-box/MEF2 domain of MEF2A bound to DNA and its implication for myocardin recruitment.

Journal of Molecular Biology
Yongqing WuLin Chen

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...Continue Reading

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Citations

Mar 8, 2012·Nucleic Acids Research·Nimanthi JayathilakaLin Chen
Nov 13, 2014·Iranian Red Crescent Medical Journal·Ali Mohammad ForoughmandKhadije Golabgirkhademi
Feb 4, 2016·Biophysical Journal·Chuanying Chen, B Montgomery Pettitt
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Feb 27, 2018·Journal of Molecular Biology·Xiao LeiLin Chen
May 30, 2021·Journal of Biological Research·Gangxu ShenWei-Lung Wang

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