6byy
From Proteopedia
MEF2 CHIMERA/DNA Complex
Structural highlights
Disease[MEF2A_HUMAN] Defects in MEF2A are a cause of coronary artery disease, autosomal dominant, type 1 (ADCAD1) [MIM:608320]. A common heart disease characterized by reduced or absent blood flow in one or more of the arteries that encircle and supply the heart. Its most important complication is acute myocardial infarction. Function[MEF2A_HUMAN] Transcriptional activator which binds specifically to the MEF2 element, 5'-YTA[AT](4)TAR-3', found in numerous muscle-specific genes. Also involved in the activation of numerous growth factor- and stress-induced genes. Mediates cellular functions not only in skeletal and cardiac muscle development, but also in neuronal differentiation and survival. Plays diverse roles in the control of cell growth, survival and apoptosis via p38 MAPK signaling in muscle-specific and/or growth factor-related transcription. In cerebellar granule neurons, phosphorylated and sumoylated MEF2A represses transcription of NUR77 promoting synaptic differentiation.[1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedMEF2B is a major target of somatic mutations in non-Hodgkin lymphoma. Most of these mutations are non-synonymous substitutions of surface residues in the MADS-box/MEF2 domain. Among them, D83V is the most frequent mutation found in tumor cells. The link between this hotspot mutation and cancer is not well understood. Here we show that the D83V mutation induces a dramatic alpha-helix to beta-strand switch in the MEF2 domain. Located in an alpha-helix region rich in beta-branched residues, the D83V mutation not only removes the extensive helix stabilization interactions but also introduces an additional beta-branched residue that further shifts the conformation equilibrium from alpha-helix to beta-strand. Cross-database analyses of cancer mutations and chameleon sequences revealed a number of well-known cancer targets harboring beta-strand favoring mutations in chameleon alpha-helices, suggesting a commonality of such conformational switch in certain cancers and a new factor to consider when stratifying the rapidly expanding cancer mutation data. The cancer mutation D83V induces an alpha-helix to beta-strand conformation switch in MEF2B.,Lei X, Kou Y, Fu Y, Rajashekar N, Shi H, Wu F, Xu J, Luo Y, Chen L J Mol Biol. 2018 Feb 22. pii: S0022-2836(18)30085-8. doi:, 10.1016/j.jmb.2018.02.012. PMID:29477338[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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