結合核小體的SWI/SNF染色質重塑複合物RSC結構獲解析
作者：
小柯機器人發布時間：2020/3/22 21:09:13
德國馬克斯普朗克生物物理化學研究所Patrick Cramer課題組取得一項新進展。他們的最新工作揭示了SWI/SNF染色質重塑複合物RSC與核小體結合後的結構。2020年3月11日，《自然》雜誌在線發表了這項成果。
研究人員報導了與核小體底物結合的RSC冷凍電鏡結構。該結構揭示RSC形成五個蛋白質模塊，並提示了重塑機制的關鍵特徵。主體模塊充當了四個可變模塊的支架，即DNA相互作用模塊、ATP酶模塊、手臂模塊和肌動蛋白相關蛋白（ARP）模塊。DNA相互作用模塊結合核外DNA，並參與識別影響RSC功能的啟動子DNA元件。ATP酶和手臂模塊分別將帶有Snf2 ATP偶聯（SnAC）結構域和指螺旋的核小體夾在中間。ATP酶模塊的轉位酶馬達在超螺旋位置+2處與核小體的邊緣接合。移動式ARP模塊可能調節轉位酶與核小體的相互作用，從而調節RSC活性。RSC核小體結構為了解NDR的形成以及人類SWI/SNF複合物的結構和功能提供了基礎，並且SWI/SNF複合物在癌症中經常發生突變。
據介紹，SWI/SNF家族的染色質重塑複合物工作於核小體減少、轉錄活躍的啟動子區域（NDR）。在釀酒酵母中，生存必需的SWI/SNF複合物RSC包含16個亞基，包括ATP依賴的DNA轉位酶Sth1。RSC從啟動子區域去除核小體，並將專門的+1和-1核小體定位於NDR兩側。
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