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  Structure of the Mediator head module

Larivière, L., Plaschka, C., Seizl, M., Wenzeck, L., Kurth, F., & Cramer, P. (2012). Structure of the Mediator head module. Nature, 492(7429), 448-451. doi:10.1038/nature11670.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0015-3C90-C Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-8433-9
Genre: Journal Article

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 Creators:
Larivière, L., Author
Plaschka, C., Author
Seizl, M., Author
Wenzeck, L., Author
Kurth, F., Author
Cramer, P.1, Author              
Affiliations:
1Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_1863498              

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Free keywords: X-ray-crystallography
 Abstract: Gene transcription by RNA polymerase (Pol) II requires the coactivator complex Mediator. Mediator connects transcriptional regulators and Pol II, and is linked to human disease1–4. Mediator from the yeast Saccharomyces cerevisiae has a molecular mass of 1.4 megadaltons and comprises 25 subunits that form the head, middle, tail and kinase modules5–7. The head module constitutes one-half of the essential Mediator core8, and comprises the conserved9 subunits Med6, Med8, Med11, Med17, Med18, Med20 and Med22. Recent X-ray analysis of the S. cerevisiae head module at 4.3A˚ resolution led to a partial architectural model with three submodules called neck, fixed jaw and moveable jaw10. Here we determine de novo the crystal structure of the head module from the fission yeast Schizosaccharomyces pombe at 3.4A˚ resolution. Structure solution was enabled by new structures of Med6 and the fixed jaw, and previous structures of the moveable jaw11 and part of the neck12, and required deletion of Med20. The S. pombe head module resembles the head of a crocodile with eight distinct elements, of which at least four are mobile. The fixed jaw comprises tooth and nose domains, whereas the neck submodule contains a helical spine and one limb, with shoulder, arm and finger elements. The arm and the essential shoulder contact other parts of Mediator. The jaws and a central joint are implicated in interactions with Pol II and its carboxy-terminal domain, and the joint is required for transcription in vitro. The S. pombe head module structure leads to a revised model of the S. cerevisiae module, reveals a high conservation and flexibility, explains knownmutations, and provides the basis for unravelling a central mechanism of gene regulation.

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Language(s): eng - English
 Dates: 2012-10-312012-12-20
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1038/nature11670
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Title: Nature
Source Genre: Journal
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Pages: - Volume / Issue: 492 (7429) Sequence Number: - Start / End Page: 448 - 451 Identifier: -