Structure of the Mediator head module

Lariviere, Laurent, Plaschka, Clemens, Seizl, Martin, Wenzeck, Larissa, Kurth, Fabian and Cramer, Patrick (2012) Structure of the Mediator head module. Nature, 492 7429: 448-451. doi:10.1038/nature11670

Author Lariviere, Laurent
Plaschka, Clemens
Seizl, Martin
Wenzeck, Larissa
Kurth, Fabian
Cramer, Patrick
Title Structure of the Mediator head module
Journal name Nature   Check publisher's open access policy
ISSN 0028-0836
Publication date 2012-12-20
Sub-type Letter to editor, brief commentary or brief communication
DOI 10.1038/nature11670
Open Access Status Not Open Access
Volume 492
Issue 7429
Start page 448
End page 451
Total pages 4
Place of publication London, United Kingdom
Publisher Nature
Language eng
Formatted 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 disease. Mediator from the yeast Saccharomyces cerevisiae has a molecular mass of 1.4megadaltons and comprises 25subunits that form the head, middle, tail and kinase modules. The head module constitutes one-half of the essential Mediator core, and comprises the conserved subunits Med6, Med8, Med11, Med17, Med18, Med20 and Med22. Recent X-ray analysis of the S. cerevisiae head module at 4.3Å resolution led to a partial architectural model with three submodules called neck, fixed jaw and moveable jaw. Here we determine de novo the crystal structure of the head module from the fission yeast Schizosaccharomyces pombe at 3.4Å resolution. Structure solution was enabled by new structures of Med6 and the fixed jaw, and previous structures of the moveable jaw and part of the neck, 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 PolII 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 known mutations, and provides the basis for unravelling a central mechanism of gene regulation.
Keyword X-ray crystallography
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Letter to editor, brief commentary or brief communication
Collection: Institute for Molecular Bioscience - Publications
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