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Crystal Structure of Apo MEF2B Reveals New Insights in DNA Binding and Cofactor Interaction
Biochemistry ( IF 2.9 ) Pub Date : 2018-06-26 00:00:00 , DOI: 10.1021/acs.biochem.8b00439
Xiao Lei 1 , Haoran Shi 1 , Yi Kou 1, 2, 3 , Niroop Rajashekar 1 , Fang Wu 4 , Chandani Sen 1 , Jiang Xu 1, 2, 3 , Lin Chen 1, 2, 3
Affiliation  

The myocyte enhancer factor 2 (MEF2) family of transcription factors plays important roles in developmental processes and adaptive responses. Although MEF2 proteins are known to bind DNA in the nucleus to regulate specific gene expression, there are reports that show that MEF2 also functions in the cytoplasm. Previous structural studies of MEF2 focused exclusively on DNA-bound MEF2 with and without various corepressors or coactivators. While these studies have established a comprehensive structural model of DNA recognition and cofactor recruitment by MEF2, the structure of MEF2 not bound to DNA, which include cytoplasmic MEF2 and free MEF2 in the nucleus, is unknown. Here we determined the structure of the MADS-box/MEF2 domain of MEF2B without DNA nor cofactor. The Apo structure of MEF2B reveals a largely preformed DNA binding interface that may be important for recognizing the shape of DNA from the minor groove side. In addition, our structure also reveals that the C-terminal helix of the MEF2-specific domain could flip up to bind to the hydrophobic groove that serves as the binding sites of MEF2 transcription cofactors. These observations shed new insights into DNA binding and cofactor interaction by MEF2 proteins.

中文翻译:

Apo MEF2B的晶体结构揭示了DNA结合和辅因子相互作用的新见解。

肌细胞增强因子2(MEF2)家族的转录因子在发育过程和适应性反应中起着重要作用。尽管已知MEF2蛋白与细胞核中的DNA结合以调节特定基因的表达,但有报道表明MEF2在细胞质中也起作用。以前对MEF2的结构研究仅集中在有和没有各种共加压因子或共激活因子的DNA结合的MEF2上。尽管这些研究已经建立了通过MEF2识别DNA和辅助因子募集的综合结构模型,但未知的未与DNA结合的MEF2的结构,包括细胞质MEF2和细胞核中的游离MEF2。在这里,我们确定了没有DNA或辅因子的MEF2B的MADS-box / MEF2结构域的结构。MEF2B的Apo结构揭示了很大程度上形成的DNA结合界面,这对于从小沟侧识别DNA的形状可能很重要。此外,我们的结构还揭示了MEF2特异性结构域的C末端螺旋可能会向上翻转以结合至疏水沟,该疏水沟充当MEF2转录辅因子的结合位点。这些发现为MEF2蛋白与DNA结合和辅因子相互作用提供了新的见解。
更新日期:2018-06-26
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