与DNA结合的CSL-Notch-Mastermind三元复合物的晶体结构。

Crystal structure of the CSL-Notch-Mastermind ternary complex bound to DNA.

作者信息

Wilson Jeffrey J, Kovall Rhett A

机构信息

Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.

出版信息

Cell. 2006 Mar 10;124(5):985-96. doi: 10.1016/j.cell.2006.01.035.

DOI:10.1016/j.cell.2006.01.035

PMID:16530045

Abstract

Notch signaling mediates communication between cells and is essential for proper embryonic patterning and development. CSL is a DNA binding transcription factor that regulates transcription of Notch target genes by interacting with coregulators. Transcriptional activation requires the displacement of corepressors from CSL by the intracellular portion of the receptor Notch (NotchIC) and the recruitment of the coactivator protein Mastermind to the complex. Here we report the 3.1 A structure of the ternary complex formed by CSL, NotchIC, and Mastermind bound to DNA. As expected, the RAM domain of Notch interacts with the beta trefoil domain of CSL; however, the C-terminal domain of CSL has an unanticipated central role in the interface formed with the Notch ankyrin repeats and Mastermind. Ternary complex formation induces a substantial conformational change within CSL, suggesting a molecular mechanism for the conversion of CSL from a repressor to an activator.

摘要

Notch信号传导介导细胞间通讯，对胚胎正常模式形成和发育至关重要。CSL是一种DNA结合转录因子，通过与共调节因子相互作用来调控Notch靶基因的转录。转录激活需要受体Notch的细胞内部分（NotchIC）将共抑制因子从CSL上置换下来，并将共激活蛋白Mastermind招募到复合物中。在此，我们报道了由CSL、NotchIC和与DNA结合的Mastermind形成的三元复合物的3.1埃结构。正如预期的那样，Notch的RAM结构域与CSL的β三叶结构域相互作用；然而，CSL的C末端结构域在与Notch锚蛋白重复序列和Mastermind形成的界面中发挥了意想不到的核心作用。三元复合物的形成在CSL内诱导了显著的构象变化，这提示了CSL从抑制因子转变为激活因子的分子机制。