Crystal Structure of the COMPASS H3K4 Methyltransferase Catalytic Module.
Crystal Structure of the COMPASS H3K4 Methyltransferase Catalytic Module.
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DOI：
10.1016/j.cell.2018.06.038
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发表时间：
2018-08-23
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：
Hsu PL;Li H;Lau HT;Leonen C;Dhall A;Ong SE;Chatterjee C;Zheng N
组蛋白甲基转移酶SET1/MLL家族在真核生物中是保守的，通过催化组蛋白H3K4单甲基化、双甲基化和三甲基化来调节转录。这些酶形成一个共同的五亚单位催化核心，其组装对其基础和调控的酶活性至关重要，其机制未知。在这里，我们介绍了完整的酵母COMPASS组蛋白甲基转移酶催化模块的晶体结构，由Swd1，Swd3，Bre2，Sdc1和Set1组成。该复合体由Swd1组成，其保守的C-末端尾部不仅核Swd3和Bre2-Sdc1亚复合体，而且与Set1相连，在催化位点附近构建了一个调控口袋。这个亚基间口袋是Swd3中一个以前未被识别的酶调节基序的靶标，它的特点是门堵式的机制，决定了SET1/MLL家族成员之间的底物选择性。通过空间定位COMPASS的功能成分，我们的结果为理解H3K4甲基转移酶家族的多方面功能和调控提供了一个结构框架。酵母COMPASS组蛋白甲基转移酶催化模块的晶体结构揭示了决定底物选择性的门堵式机制
The SET1/MLL family of histone methyltransferases are conserved in eukaryotes and regulate transcription by catalyzing histone H3K4 mono-, di-, and tri-methylation. These enzymes form a common five-subunit catalytic core, whose assembly is critical for their basal and regulated enzymatic activities through unknown mechanisms. Here we present the crystal structure of the intact yeast COMPASS histone methyltransferase catalytic module, consisting of Swd1, Swd3, Bre2, Sdc1, and Set1. The complex is organized by Swd1, whose conserved C-terminal tail not only nucleates Swd3 and a Bre2-Sdc1 subcomplex, but also joins Set1 to construct a regulatory pocket next to the catalytic site. This inter-subunit pocket is targeted by a previously unrecognized enzyme-modulating motif in Swd3 and features a doorstop-style mechanism dictating substrate selectivity among SET1/MLL family members. By spatially mapping the functional components of COMPASS, our results provide a structural framework for understanding the multifaceted functions and regulation of the H3K4 methyltransferase family. The crystal structure of the yeast COMPASS histone methyltransferase catalytic module reveals a doorstop-style mechanism dictating substrate selectivity
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影响因子：
30.8
作者：
通讯作者：
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MLL家族甲基转移酶活性调节的结构基础
影响因子：
64.8
作者：
Li, Yanjing;Han, Jianming;Zhang, Yuebin;Cao, Fang;Liu, Zhijun;Li, Shuai;Wu, Jian;Hu, Chunyi;Wang, Yan;Shuai, Jin;Chen, Juan;Cao, Liaoran;Li, Dangsheng;Shi, Pan;Tian, Changlin;Zhang, Jian;Dou, Yali;Li, Guohui;Chen, Yong;Lei, Ming
通讯作者：
Lei, Ming
影响因子：
5.7
作者：
Avdic, Vanja;Zhang, Pamela;Couture, Jean-Francois
通讯作者：
Couture, Jean-Francois
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
4.8
作者：
Krogan, NJ;Dover, J;Shilatifard, A
通讯作者：
Shilatifard, A