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转录共激活复合物SAGA的结构获解析
2020-01-29 16:30

德国马克斯-普朗克学会生物物理化学研究所Patrick Cramer团队解析了转录共激活复合物SAGA的结构。该研究2020年1月22日在线发表于国际一流学术期刊《自然》。

研究人员报道了来自酿酒酵母的SAGA的冷冻电镜结构,并以3.3Å的分辨率解析了核心模块。核心模块由Taf5、Sgf73和Spt20亚基和组蛋白八聚体样折叠组成。八聚体样折叠包含了异二聚体Taf6–Taf9、Taf10–Spt7和Taf12–Ada1,以及Spt3中的两个组蛋白折叠结构域。Spt3和相邻的亚基Spt8与TATA盒结合蛋白(TBP)相互作用。TFIID中的八聚体样折叠及其与TBP相互作用的区域相似,而Taf5和Taf6 HEAT结构域采用不同的构象。Taf12和Spt20与Tra1模块形成灵活的连接,而Sgf73与DUB模块捆绑在一起。核小体与SAGA的结合将HAT和DUB模块从核心模块表面移开,从而允许DUB模块结合泛素化核小体的表面。

据了解,RNA聚合酶II介导的基因转录受激活蛋白的调控,该蛋白募集了SAGA(Spt–Ada–Gcn5–乙酰转移酶)和转录因子IID(TFIID)。SAGA是所有调控转录所必需的,并在真核生物中是保守的。SAGA包含四个模块:激活剂结合Tra1模块、核心模块、组蛋白乙酰转移酶(HAT)模块和组蛋白去泛素化(DUB)模块。先前的研究提供了部分结构,但中央核心模块的结构尚不清楚。

附:英文原文

Title: Structure of the transcription coactivator SAGA

Author: Haibo Wang, Christian Dienemann, Alexandra Sttzer, Henning Urlaub, Alan C. M. Cheung, Patrick Cramer

Issue&Volume: 2020-01-22

Abstract: Gene transcription by RNA polymerase II is regulated by activator proteins that recruit the coactivator complexes SAGA (Spt–Ada–Gcn5–acetyltransferase)1,2 and transcription factor IID (TFIID)2,3,4. SAGA is required for all regulated transcription5 and is conserved among eukaryotes6. SAGA contains four modules7,8,9: the activator-binding Tra1 module, the core module, the histone acetyltransferase (HAT) module and the histone deubiquitination (DUB) module. Previous studies provided partial structures10,11,12,13,14, but the structure of the central core module is unknown. Here we present the cryo-electron microscopy structure of SAGA from the yeast Saccharomyces cerevisiae and resolve the core module at 3.3 resolution. The core module consists of subunits Taf5, Sgf73 and Spt20, and a histone octamer-like fold. The octamer-like fold comprises the heterodimers Taf6–Taf9, Taf10–Spt7 and Taf12–Ada1, and two histone-fold domains in Spt3. Spt3 and the adjacent subunit Spt8 interact with the TATA box-binding protein (TBP)2,7,15,16,17. The octamer-like fold and its TBP-interacting region are similar in TFIID, whereas Taf5 and the Taf6 HEAT domain adopt distinct conformations. Taf12 and Spt20 form flexible connections to the Tra1 module, whereas Sgf73 tethers the DUB module. Binding of a nucleosome to SAGA displaces the HAT and DUB modules from the core-module surface, allowing the DUB module to bind one face of an ubiquitinated nucleosome.

DOI: 10.1038/s41586-020-1933-5

Source: https://www.nature.com/articles/s41586-020-1933-5

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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