3rj1
Architecture of the Mediator Head moduleArchitecture of the Mediator Head module
Structural highlights
FunctionMED17_YEAST Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. The Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins.[1] [2] [3] [4] [5] Publication Abstract from PubMedMediator is a key regulator of eukaryotic transcription, connecting activators and repressors bound to regulatory DNA elements with RNA polymerase II (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 tail. 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 angstroms. 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. Architecture of the Mediator head module.,Imasaki T, Calero G, Cai G, Tsai KL, Yamada K, Cardelli F, Erdjument-Bromage H, Tempst P, Berger I, Kornberg GL, Asturias FJ, Kornberg RD, Takagi Y Nature. 2011 Jul 3;475(7355):240-3. doi: 10.1038/nature10162. PMID:21725323[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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