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徐彦辉团队解析人类中介体和中介体结合的起始前复合物结构
作者:小柯机器人 发布时间:2021/5/8 16:11:55

复旦大学徐彦辉研究团队解析出人类中介体和中介体结合的起始前复合物结构。这一研究成果于2021年5月6日在线发表在国际学术期刊《科学》上。

研究人员表示,1.3 MDa转录因子IID(TFIID)是起始前复合物(PIC)组装和几乎所有基因上RNA聚合酶II(Pol II)介导的转录起始所必需的。26个亚基的中介体促进转录和细胞周期蛋白依赖性激酶7(CDK7)介导的Pol II C末端域(CTD)磷酸化。

研究人员确定了人类中介体的结构在扩展的尾巴模块(近原子分辨率)和弯曲的尾巴构象以及基于TFIID的PIC中介体(76个多肽,?4.1 MDa)在四个不同的构象中的结构。PIC-中介体组装引起中介体的协调重组,并产生头部-中部的三明治结构,这能够稳定两个CTD片段并将CTD带入CDK7进行磷酸化,从而提示CTD门控机制有利于磷酸化。基于TFIID的PIC体系结构可调节中介体的组织和TFIIH的稳定性,从而突出了TFIID在介导PIC-中介体组装中的重要性。

附:英文原文

Title: Structures of the human Mediator and Mediator-bound preinitiation complex

Author: Xizi Chen, Xiaotong Yin, Jiabei Li, Zihan Wu, Yilun Qi, Xinxin Wang, Weida Liu, Yanhui Xu

Issue&Volume: 2021/05/06

Abstract: The 1.3-MDa transcription factor IID (TFIID) is required for preinitiation complex (PIC) assembly and RNA polymerase II (Pol II)-mediated transcription initiation on almost all genes. The 26-subunit Mediator stimulates transcription and cyclin-dependent kinase 7 (CDK7)-mediated phosphorylation of Pol II C-terminal domain (CTD). We determined the structures of human Mediator in the Tail module-extended (at near-atomic resolution) and Tail-bent conformations and structures of TFIID-based PIC-Mediator (76 polypeptides, ~4.1 MDa) in four distinct conformations. PIC-Mediator assembly induces concerted reorganization (Head-tilting and Middle-down) of Mediator and creates a Head-Middle sandwich, which stabilizes two CTD segments and brings CTD to CDK7 for phosphorylation, suggesting a CTD-gating mechanism favorable for phosphorylation. The TFIID-based PIC architecture modulates Mediator organization and TFIIH stabilization, underscoring the significance of TFIID in orchestrating PIC-Mediator assembly.

DOI: 10.1126/science.abg0635

Source: https://science.sciencemag.org/content/early/2021/05/05/science.abg0635

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037