Structural basis for assembly and activation of the heterotetrameric SAGA histone H2B deubiquitinase module.
Structural basis for assembly and activation of the heterotetrameric SAGA histone H2B deubiquitinase module.
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DOI：
10.1016/j.cell.2010.04.026
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发表时间：
2010-05-14
期刊：
影响因子：
64.5
通讯作者：
Zheng N
中科院分区：
文献类型：
--
作者：
Köhler A;Zimmerman E;Schneider M;Hurt E;Zheng N
去泛素化酶（DUBs）通过从特定的蛋白质底物上切割泛素来调节多种细胞功能。它们的活动如何在各种细胞环境中调节仍然知之甚少。酵母去泛素化酶Ubp 8蛋白被佐贺复合物募集并激活，与Sgf 11、Sus 1和Sgf 73一起形成DUB模块，负责在基因表达期间去泛素化组蛋白H2 B。在这里，我们报告了完整的佐贺DUB模块的晶体结构，该模块具有由Sgf 73在结构上耦合的两个功能性裂片。在“装配叶”中，一个长的Sgf 11 N-末端螺旋被Sus 1夹在Ubp 8 ZnF-UBP结构域上。在“催化叶”中，Sgf 11 C-末端锌指结构域结合到其活性位点旁边的Ubp 8催化结构域。我们的结构和功能分析揭示了Sgf 11和Sgf 73在激活Ubp 8去泛素化组蛋白H2 B中的核心作用，并展示了DUB如何通过其非底物伙伴进行变构调节。
Deubiquitinating enzymes (DUBs) regulate diverse cellular functions by cleaving ubiquitin from specific protein substrates. How their activities are modulated in various cellular contexts remains poorly understood. The yeast deubiquitinase Ubp8 protein is recruited and activated by the SAGA complex and, together with Sgf11, Sus1, and Sgf73, forms a DUB module responsible for deubiquitinating histone H2B during gene expression. Here we report the crystal structure of the complete SAGA DUB module, which features two functional lobes structurally coupled by Sgf73. In the “assembly lobe”, a long Sgf11 N-terminal helix is clamped onto the Ubp8 ZnF-UBP domain by Sus1. In the “catalytic lobe”, an Sgf11 C-terminal zinc finger domain binds to the Ubp8 catalytic domain next to its active site. Our structural and functional analyses reveal a central role of Sgf11 and Sgf73 in activating Ubp8 for deubiquitinating histone H2B and demonstrate how a DUB can be allosterically regulated by its non-substrate partners.
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影响因子：
9.8
作者：
Helmlinger D;Hardy S;Abou-Sleymane G;Eberlin A;Bowman AB;Gansmüller A;Picaud S;Zoghbi HY;Trottier Y;Tora L;Devys D
通讯作者：
Devys D
影响因子：
16
作者：
Jani, Divyang;Lutz, Sheila;Marshall, Neil J.;Fischer, Tamas;Koehler, Alwin;Ellisdon, Andrew M.;Hurt, Ed;Stewart, Murray
通讯作者：
Stewart, Murray
影响因子：
16
作者：
Cohn, Martin A.;Kowal, Przemyslaw;D'Andrea, Alan D.
通讯作者：
D'Andrea, Alan D.
影响因子：
4.8
作者：
Daniel, JA;Torok, MS;Grant, PA
通讯作者：
Grant, PA
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL