Structural basis for histone H2B deubiquitination by the SAGA DUB module.
Structural basis for histone H2B deubiquitination by the SAGA DUB module.
复制标题
DOI：
10.1126/science.aac5681
复制
发表时间：
2016-02-12
期刊：
影响因子：
--
通讯作者：
Wolberger C
中科院分区：
文献类型：
--
作者：
Morgan MT;Haj-Yahya M;Ringel AE;Bandi P;Brik A;Wolberger C
单泛素化组蛋白H2 B在转录激活中发挥多种作用。H2 B被Spt-Ada-Gcn 5乙酰转移酶（佐贺）共激活剂去泛素化，该共激活剂含有一个被称为去泛素化（DUB）模块的四蛋白亚复合物。与泛素化核小体结合的Ubp 8/Sgf 11/Sus 1/Sgf 73 DUB模块的晶体结构显示DUB模块主要接触H2 A/H2 B，Sgf 11锌指结构域上的精氨酸簇对接在保守的H2 A/H2 B酸性补丁上。Ubp 8催化结构域介导与H2 B以及与缀合的泛素的额外接触。我们发现，DUB模块deubiquitinates H2 B的背景下，核小体和H2 A/H2 B二聚体与组蛋白伴侣，FACT复合，表明佐贺可以靶向H2 B在多个阶段的核小体拆卸和重组在转录过程中。
Monoubiquitinated histone H2B plays multiple roles in transcription activation. H2B is deubiquitinated by the Spt-Ada-Gcn5 acetyltransferase (SAGA) coactivator, which contains a four-protein subcomplex known as the deubiquitinating (DUB) module. The crystal structure of the Ubp8/Sgf11/Sus1/Sgf73 DUB module bound to a ubiquitinated nucleosome reveals that the DUB module primarily contacts H2A/H2B, with an arginine cluster on the Sgf11 zinc finger domain docking on the conserved H2A/H2B acidic patch. The Ubp8 catalytic domain mediates additional contacts with H2B, as well as with the conjugated ubiquitin. We find that the DUB module deubiquitinates H2B both in the context of the nucleosome and in H2A/H2B dimers complexed with the histone chaperone, FACT, suggesting that SAGA could target H2B at multiple stages of nucleosome disassembly and reassembly during transcription.