Cryo-EM structure of the Saccharomyces cerevisiae Rpd3L histone deacetylase complex.
Cryo-EM structure of the Saccharomyces cerevisiae Rpd3L histone deacetylase complex.
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DOI：
10.1038/s41467-023-38687-z
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发表时间：
2023-05-27
影响因子：
16.6
通讯作者：
He, Yuan
中科院分区：
文献类型：
--
作者：
Patel, Avinash B.;Qing, Jinkang;Tam, Kelly H.;Zaman, Sara;Luiso, Maria;Radhakrishnan, Ishwar;He, Yuan
Rpd3L组蛋白脱乙酰酶(HDAC)复合体是一个古老的12亚基复合体，广泛存在于真核生物中，在DNA结合因子的募集部位或附近进行局部脱乙酰化。在这里，我们描述了这个原型HDAC复合体的低温EM结构，其特征是多达七个亚基为唯一的催化亚基Rpd3的紧密整合起到了支架作用。主要的支架蛋白Sin3、Rpd3和组蛋白伴侣Ume1以两个副本的形式存在，每个副本组织成不对称二聚体分子组装的单独的叶。一个Rpd3的活性部位被Rxt2的亮氨酸侧链完全封闭，而两个叶的尖端和更外围的亚单位表现出不同程度的灵活性和位置紊乱。该结构揭示了真菌和哺乳动物复合体中无关亚基之间的意外结构同源性/相似性，为深入了解这些复合体的结构、生物学和机制以及发现HDAC复合体特异性抑制剂提供了基础。Rpd3L HDAC复合体是一种古老的染色质修饰复合体，存在于多种真核生物中。在这里，作者描述了酵母复合体的低温EM结构，并表明关键特征在人类复合体中得到保留。
The Rpd3L histone deacetylase (HDAC) complex is an ancient 12-subunit complex conserved in a broad range of eukaryotes that performs localized deacetylation at or near sites of recruitment by DNA-bound factors. Here we describe the cryo-EM structure of this prototypical HDAC complex that is characterized by as many as seven subunits performing scaffolding roles for the tight integration of the only catalytic subunit, Rpd3. The principal scaffolding protein, Sin3, along with Rpd3 and the histone chaperone, Ume1, are present in two copies, with each copy organized into separate lobes of an asymmetric dimeric molecular assembly. The active site of one Rpd3 is completely occluded by a leucine side chain of Rxt2, while the tips of the two lobes and the more peripherally associated subunits exhibit varying levels of flexibility and positional disorder. The structure reveals unexpected structural homology/analogy between unrelated subunits in the fungal and mammalian complexes and provides a foundation for deeper interrogations of structure, biology, and mechanism of these complexes, as well as for the discovery of HDAC complex-specific inhibitors. The Rpd3L HDAC complex is an ancient chromatin-modifying complex found in diverse eukaryotes. Here, authors describe the cryo-EM structure of the yeast complex and show that key features are preserved in the human complex.
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DOI：
10.1107/s2059798318009324
发表时间：
2018-09-01
期刊：
Acta crystallographica. Section D, Structural biology
影响因子：
--
作者：
Afonine PV;Klaholz BP;Moriarty NW;Poon BK;Sobolev OV;Terwilliger TC;Adams PD;Urzhumtsev A
通讯作者：
Urzhumtsev A
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
3.7
作者：
Sardiu ME;Gilmore JM;Carrozza MJ;Li B;Workman JL;Florens L;Washburn MP
通讯作者：
Washburn MP
DOI：
10.1042/bcj20210708
发表时间：
2021-12-22
期刊：
The Biochemical journal
影响因子：
--
作者：
Kimanius D;Dong L;Sharov G;Nakane T;Scheres SHW
通讯作者：
Scheres SHW
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K