近日,复旦大学徐彦辉小组报道了核小体结合的人BAF复合物结构。2020年1月30日,国际知名学术期刊《科学》在线发表了这一成果。
研究人员报道了结合核小体的人BAF复合物的3.7Å分辨率冷冻电镜结构,从而揭示核小体被碱基和ATPase模块夹在中间,后者被肌动蛋白相关蛋白(ARP)模块桥接。ATP酶马达位于核小体DNA的近端,并且在ATP水解后将与核小体结合并沿其泵送DNA。SMARCB1的C端α螺旋富含在癌症中经常突变的正电荷残基,它介导与核小体的酸性斑块的相互作用。ARID1A和SMARCC分别是基础模块组织中的结构核心和支架。这项研究为人类BAF复合物的亚基组织和核小体识别提供了结构上的了解。
据悉,哺乳动物SWI/SNF家族的染色质重塑复合物BAF和PBAF调节染色质的结构和转录,其突变与癌症有关。
附:英文原文
Author: Shuang He, Zihan Wu, Yuan Tian, Zishuo Yu, Jiali Yu, Xinxin Wang, Jie Li, Bijun Liu, Yanhui Xu
Issue&Volume: 2020/01/30
Abstract: AbstractMammalian SWI/SNF family chromatin remodelers, BAF and PBAF, regulate chromatin structure and transcription, with their mutations linked to cancers. The 3.7 -resolution cryo-EM structure of human BAF bound to nucleosome reveals that the nucleosome is sandwiched by the Base and the ATPase modules, which are bridged by the actin-related protein (ARP) module. The ATPase motor is positioned proximal to nucleosomal DNA and, upon ATP hydrolysis, would engage with and pump DNA along the nucleosome. The C-terminal α-helix of SMARCB1, enriched in positively charged residues frequently mutated in cancers, mediates interactions with an acidic patch of nucleosome. ARID1A and SMARCC serve as a structural core and scaffold in the Base module organization, respectively. Our study provides structural insights into subunit organization and nucleosome recognition of human BAF complex.
DOI: 10.1126/science.aaz9761
Source: https://science.sciencemag.org/content/early/2020/01/29/science.aaz9761