Lei Xiao, Shi Haoran, Kou Yi, Rajashekar Niroop, Wu Fang, Sen Chandani, Xu Jiang, Chen Lin
Molecular and Computational Biology, Department of Biological Sciences , University of Southern California , Los Angeles , California 90089 , United States.
Department of Chemistry , University of Southern California , Los Angeles , California 90089 , United States.
Biochemistry. 2018 Jul 17;57(28):4047-4051. doi: 10.1021/acs.biochem.8b00439. Epub 2018 Jul 5.
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.
转录因子的肌细胞增强因子2（MEF2）家族在发育过程和适应性反应中发挥着重要作用。虽然已知MEF2蛋白在细胞核中与DNA结合以调节特定基因表达，但有报道表明MEF2在细胞质中也发挥作用。先前对MEF2的结构研究仅专注于结合有或没有各种共抑制因子或共激活因子的DNA结合型MEF2。虽然这些研究已经建立了MEF2识别DNA和募集辅助因子的全面结构模型，但未结合DNA的MEF2的结构，包括细胞质中的MEF2和细胞核中的游离MEF2，仍然未知。在这里，我们确定了没有DNA和辅助因子的MEF2B的MADS盒/MEF2结构域的结构。MEF2B的无配体结构揭示了一个基本预先形成的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，我们的结构还表明，MEF2特异性结构域的C末端螺旋可以翻转起来与作为MEF2转录辅助因子结合位点的疏水凹槽结合。这些观察结果为MEF2蛋白的DNA结合和辅助因子相互作用提供了新的见解。
