Crystal structure of the PRC1 ubiquitylation module bound to the nucleosome

摘要

Polycomb类蛋白抑制高等真核生物由发育调控的基因的表达。“Polycomb抑制复合物-1”(PRC1)能够利用E3泛素连接酶亚单元Ring 1B和Bmi1再加上一种E2泛素结合酶UbcH5c将组蛋白H2A泛素化。在这篇论文中，Song Tan及同事描述了与其核小体核心基质结合在一起的PRC1泛素化模块的晶体结构。该结构显示了一种组蛋白修饰酶是怎样通过与在空间上跟催化点截然不同的多个核小体表面发生相互作用来实现基质特异性的，也揭示了E2酶在基质识别中所起的一个未曾料到的作用。基于他们的新数据，作者生成了关于相关BRCA1 H2A E3连接酶与核小体之结合的一个模型，该模型可被用来研究BRCA1的组蛋白修饰活性在发育和癌症易感性中所起的作用。%The Polycomb group of epigenetic enzymes represses expression of developmentally regulated genes in many eukaryotes. This group includes the Polycomb repressive complex 1 (PRC1), which ubiquitylates nucleosomal histone H2A Lys 119 using its E3 ubiquitin ligase subunits, Ring1B and Bmi1, together with an E2 ubiquitin-conjugating enzyme, UbcH5c. However, the molecular mechanism of nucleosome substrate recognition by PRC1 or other chromatin enzymes is unclear. Here we present the crystal structure of the human Ring1B - Bmi1 - UbcH5c E3-E2 complex (the PRC1 ubiquitylation module) by interacting with several nucleosome surfaces spatially distinct from the site of catalysis. Our structure further reveals an unexpected role for the ubiquitin E2 enzyme in substrate recognition, and provides insight into how the related histone H2A E3 ligase, BRCA1, interacts with and ubiquitylates the nucleosome.