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Architecture of the Mediator head module

Cobra 添加于 2011/7/5 13:55:00  2593次阅读 | 1次推荐 | 0个评论

Mediator is a key regulator of eukaryotic transcription1, connecting activators and repressors bound to regulatory DNA elements with RNA polymerase II1, 2, 3, 4 (Pol II). In the yeast Saccharomyces cerevisiae, Mediator comprises 25 subunits with a total mass of more than one megadalton (refs 5, 6) and is organized into three modules, called head, middle/arm and tail7, 8, 9. Our understanding of Mediator assembly and its role in regulating transcription has been impeded so far by limited structural information. Here we report the crystal structure of the essential Mediator head module (seven subunits, with a mass of 223 kilodaltons) at a resolution of 4.3 ångströms. Our structure reveals three distinct domains, with the integrity of the complex centred on a bundle of ten helices from five different head subunits. An intricate pattern of interactions within this helical bundle ensures the stable assembly of the head subunits and provides the binding sites for general transcription factors and Pol II. Our structural and functional data suggest that the head module juxtaposes transcription factor IIH and the carboxy-terminal domain of the largest subunit of Pol II, thereby facilitating phosphorylation of the carboxy-terminal domain of Pol II. Our results reveal architectural principles underlying the role of Mediator in the regulation of gene expression.

作 者:Tsuyoshi Imasaki; Guillermo Calero; Gang Cai; Kuang-Lei Tsai; Kentaro Yamada; Francesco Cardelli; Hediye Erdjument-Bromage; Paul Tempst; Imre Berger; Guy Lorch Kornberg; Francisco J. Asturias; Roger D. Kornberg; Yuichiro Takagi
期刊名称: Nature
期卷页: 2011-07-03 第卷 第期 ~页
学科领域:生命科学 » 遗传学与生物信息学 » 生物信息学
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原文链接:http://www.nature.com/nature/journal/vaop/ncurrent/full/nature10162.html
DOI: doi:10.1038/nature10162
ISBN: 0028-0836
关键词: Biophysics, Biochemistry, Structural biology
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