Architecture of the RNA polymerase II-Mediator core initiation complex

Architecture of the RNA polymerase II-Mediator core initiation complex
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DOI:
10.1038/nature14229
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发表时间:
2015-02-19
期刊:
影响因子:
64.8
通讯作者:
Cramer, P.
Cramer, P.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Plaschka, C.;Lariviere, L.;Cramer, P.

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保守的共激活复合物介体能够通过RNA聚合酶(Pol)II调节转录。在这里,我们重建了一个积极的15亚基核心调解人(cMed),包括所有必需的调解人亚基酿酒酵母。在9.7 A分辨率下测定与核心起始复合物结合的cMed的冷冻电子显微镜结构。cMed结合羧基末端结构域(CTD)附近的Rpb 4-Rpb 7茎周围的Pol II。Mediator头部模块结合Pol II对接物和TFIIB条带并稳定起始复合物。中介体中间模块延伸到Fol II足,具有可能影响聚合酶构象的“板”。介体亚基Medl 4在头部和中间模块之间形成“梁”,并连接到尾部模块,该尾部模块被预测为结合位于上游DNA上的转录激活因子。介体“臂”和“钩”结构域有助于“摇篮”,其可以定位CTD和TFIIH激酶以刺激Pol II磷酸化。
The conserved co-activator complex Mediator enables regulated transcription irntiation by RNA polymerase (Pol) II. Here we reconstitute an active 15-subunit core Mediator (cMed) comprising all essential Mediator subunits from Saccharomyces erevisiae. The cryo-electron microscopic structure of cMed bound to a core initiation complex was determined at 9.7 A resolution. cMed binds Pol II around the Rpb4-Rpb7 stalk near the carboxy-terminal domain (CTD). The Mediator head module binds the Pol II dock and the TFIIB ribbon and stabilizes the initiation complex. The Mediator middle module extends to the Fol II foot with a 'plank' that may influence polymerase conformation. The Mediator subunit Medl4 forms a 'beam' between the head and middle modules and connects to the tail module that is predicted to bind transcription activators located on upstream DNA. The Mediator 'arm' and 'hook' domains contribute to a 'cradle' that may position the CTD and TFIIH kinase to stimulate Pol II phosphorylation.