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结合核小体的SWI/SNF染色质重塑复合物RSC结构获解析
2020-03-12 21:09

德国马克斯普朗克生物物理化学研究所Patrick Cramer课题组取得一项新进展。他们的最新工作揭示了SWI/SNF染色质重塑复合物RSC与核小体结合后的结构。2020年3月11日,《自然》杂志在线发表了这项成果。

研究人员报道了与核小体底物结合的RSC冷冻电镜结构。该结构揭示RSC形成五个蛋白质模块,并提示了重塑机制的关键特征。主体模块充当了四个可变模块的支架,即DNA相互作用模块、ATP酶模块、手臂模块和肌动蛋白相关蛋白(ARP)模块。DNA相互作用模块结合核外DNA,并参与识别影响RSC功能的启动子DNA元件。ATP酶和手臂模块分别将带有Snf2 ATP偶联(SnAC)结构域和指螺旋的核小体夹在中间。ATP酶模块的转位酶马达在超螺旋位置+2处与核小体的边缘接合。移动式ARP模块可能调节转位酶与核小体的相互作用,从而调节RSC活性。RSC核小体结构为了解NDR的形成以及人类SWI/SNF复合物的结构和功能提供了基础,并且SWI/SNF复合物在癌症中经常发生突变。
 
据介绍,SWI/SNF家族的染色质重塑复合物工作于核小体减少、转录活跃的启动子区域(NDR)。在酿酒酵母中,生存必需的SWI/SNF复合物RSC包含16个亚基,包括ATP依赖的DNA转位酶Sth1。RSC从启动子区域去除核小体,并将专门的+1和-1核小体定位于NDR两侧。
 
附:英文原文

Title: Structure of SWI/SNF chromatin remodeller RSC bound to a nucleosome

Author: Felix R. Wagner, Christian Dienemann, Haibo Wang, Alexandra Sttzer, Dimitry Tegunov, Henning Urlaub, Patrick Cramer

Issue&Volume: 2020-03-11

Abstract: Chromatin-remodelling complexes of the SWI/SNF family function in the formation of nucleosome-depleted, transcriptionally active promoter regions (NDRs). In the yeast Saccharomyces cerevisiae, the essential SWI/SNF complex RSC contains 16 subunits, including the ATP-dependent DNA translocase Sth1. RSC removes nucleosomes from promoter regions and positions the specialized +1 and -1 nucleosomes that flank NDRs. Here we present the cryo-electron microscopy structure of RSC in complex with a nucleosome substrate. The structure reveals that RSC forms five protein modules and suggests key features of the remodelling mechanism. The body module serves as a scaffold for the four flexible modules that we call DNA-interacting, ATPase, arm and actin-related protein (ARP) modules. The DNA-interacting module binds extra-nucleosomal DNA and is involved in the recognition of promoter DNA elements that influence RSC functionality. The ATPase and arm modules sandwich the nucleosome disc with the Snf2 ATP-coupling (SnAC) domain and the finger helix, respectively. The translocase motor of the ATPase module engages with the edge of the nucleosome at superhelical location +2. The mobile ARP module may modulate translocase–nucleosome interactions to regulate RSC activity. The RSC–nucleosome structure provides a basis for understanding NDR formation and the structure and function of human SWI/SNF complexes that are frequently mutated in cancer.

DOI: 10.1038/s41586-020-2088-0

Source: https://www.nature.com/articles/s41586-020-2088-0

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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