6WC2

Crystal Structure of a Ternary MEF2 Chimera/NKX2-5/myocardin enhancer DNA Complex

6WC2 の概要

• エントリーDOI: 10.2210/pdb6wc2/pdb
• 分子名称: MEF2 Chimera,Myocyte-specific enhancer factor 2B,Myocyte-specific enhancer factor 2A, Myocardin Enhancer DNA, Homeobox protein Nkx-2.5, ... (5 entities in total)
• 機能のキーワード: transcription factor, dna binding protein, cardiogenesis, carcinogenesis, transcription
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 15
• 化学式量合計: 129719.01

構造登録者

Lei, X.,Chen, L. (登録日: 2020-03-29, 公開日: 2020-07-22, 最終更新日: 2023-10-18)

主引用文献

Lei, X.,Zhao, J.,Sagendorf, J.M.,Rajashekar, N.,Xu, J.,Dantas Machado, A.C.,Sen, C.,Rohs, R.,Feng, P.,Chen, L.
Crystal Structures of Ternary Complexes of MEF2 and NKX2-5 Bound to DNA Reveal a Disease Related Protein-Protein Interaction Interface.
J.Mol.Biol., 432:5499-5508, 2020

PubMed Abstract: MEF2 and NKX2-5 transcription factors interact with each other in cardiogenesis and are necessary for normal heart formation. Despite evidence suggesting that these two transcription factors function synergistically and possibly through direct physical interactions, molecular mechanisms by which they interact are not clear. Here we determined the crystal structures of ternary complexes of MEF2 and NKX2-5 bound to myocardin enhancer DNA in two crystal forms. These crystal structures are the first example of human MADS-box/homeobox ternary complex structures involved in cardiogenesis. Our structures reveal two possible modes of interactions between MEF2 and NKX2-5: MEF2 and NKX bind to adjacent DNA sites to recognize DNA in cis; and MEF2 and NKX bind to different DNA strands to interact with each other in trans via a conserved protein-protein interface observed in both crystal forms. Disease-related mutations are mapped to the observed protein-protein interface. Our structural studies provide a starting point to understand and further study the molecular mechanisms of the interactions between MEF2 and NKX2.5 and their roles in cardiogenesis.

PubMed: 32681840
DOI: 10.1016/j.jmb.2020.07.004

実験手法

X-RAY DIFFRACTION (2.1 Å)