Yeast PIC-Mediator structure with RNA polymerase II C-terminal domain.
Yeast PIC-Mediator structure with RNA polymerase II C-terminal domain.
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DOI：
10.1073/pnas.2220542120
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发表时间：
2023-04-11
影响因子：
11.1
通讯作者：
Cramer, Patrick
中科院分区：
文献类型：
--
作者：
Schilbach, Sandra;Wang, Haibo;Dienemann, Christian;Cramer, Patrick
关键词：
在基因启动子处，RNA聚合酶II（Pol II）组装成包括辅激活因子介体的前起始复合物（PIC）。在这里，我们描述了PIC-介体复合物从酵母在前所未有的分辨率，并提供了一个参考结构的起始复合物。我们获得的洞察力的调解员和它的相互作用与Pol II的原子细节。此外，我们观察到三个调解人结合片段的C-末端结构域（CTD）的Pol II稳定调解人构象内的PIC和显着扩展以前的信息从人类系统。这些肽区对应于几乎50%的酵母CTD，因此是细胞活力所需的最小长度。它们的位置和构象部分非常保守，突出了它们在转录中的核心作用。对于转录起始，RNA聚合酶II（Pol II）形成与一般共激活因子介体缔合的前起始复合物（PIC）。尽管已经报道了人类PIC-介体结构的原子模型，但其酵母对应物的结构仍然不完整。在这里，我们提出了一个原子模型的酵母PIC与核心调解员，包括调解员中间模块，以前解决不好，包括亚基Med 1，以前缺乏。我们观察到三个肽区含有11的26个七肽重复的灵活的C-末端重复结构域（CTD）的Pol II。这些CTD区域中的两个结合在Mediator头部和中间模块之间，并形成定义的CTD-Mediator相互作用。CTD肽1结合在Med 6肩和Med 31结结构域之间，而CTD肽2与Med 4形成额外的接触。第三个CTD区域（肽3）结合在Mediator cradle中并与Mediator hook结合。与人PIC-介体结构的比较表明，肽1中的中心区域是相似的，并与介体形成保守的接触，而肽2和3表现出不同的结构和介体相互作用。
At gene promoters, RNA polymerase II (Pol II) assembles into a preinitiation complex (PIC) which includes the coactivator Mediator. Here, we describe the PIC-Mediator complex from yeast at unprecedented resolution and provide a reference structure for initiation complexes. We obtain insights into the atomic details of Mediator and its interaction with Pol II. Moreover, we observe three Mediator-bound fragments of the C-terminal domain (CTD) of Pol II which stabilize Mediator conformation within the PIC and significantly extend prior information from the human system. These peptide regions correspond to almost 50% of the yeast CTD and thus the minimal length required for cell viability. Their location and conformation are in part extremely conserved, highlighting their central role in transcription. For transcription initiation, RNA polymerase II (Pol II) forms a preinitiation complex (PIC) that associates with the general coactivator Mediator. Whereas atomic models of the human PIC-Mediator structure have been reported, structures for its yeast counterpart remain incomplete. Here, we present an atomic model for the yeast PIC with core Mediator, including the Mediator middle module that was previously poorly resolved and including subunit Med1 that was previously lacking. We observe three peptide regions containing eleven of the 26 heptapeptide repeats of the flexible C-terminal repeat domain (CTD) of Pol II. Two of these CTD regions bind between the Mediator head and middle modules and form defined CTD–Mediator interactions. CTD peptide 1 binds between the Med6 shoulder and Med31 knob domains, whereas CTD peptide 2 forms additional contacts with Med4. The third CTD region (peptide 3) binds in the Mediator cradle and associates with the Mediator hook. Comparisons with the human PIC-Mediator structure show that the central region in peptide 1 is similar and forms conserved contacts with Mediator, whereas peptides 2 and 3 exhibit distinct structures and Mediator interactions.
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影响因子：
64.5
作者：
Robinson PJ;Trnka MJ;Bushnell DA;Davis RE;Mattei PJ;Burlingame AL;Kornberg RD
通讯作者：
Kornberg RD
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
DOI：
10.1126/science.abg3074
发表时间：
2021-04-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Abdella R;Talyzina A;Chen S;Inouye CJ;Tjian R;He Y
通讯作者：
He Y
影响因子：
64.8
作者：
Nozawa, Kayo;Schneider, Thomas R.;Cramer, Patrick
通讯作者：
Cramer, Patrick
影响因子：
56.9
作者：
Chen, Xizi;Qi, Yilun;Xu, Yanhui
通讯作者：
Xu, Yanhui