English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Core Mediator structure at 3.4 Å extends model of transcription initiation complex.

MPS-Authors
/persons/resource/persons188861

Nozawa,  K.
Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society;

/persons/resource/persons127020

Cramer,  P.
Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society;

Locator
There are no locators available
Fulltext (public)
There are no public fulltexts available
Supplementary Material (public)

2431854_Suppl_1.pdf
(Supplementary material), 377KB

2431854_Suppl_2.txt
(Supplementary material), 2MB

2431854_Suppl_3.txt
(Supplementary material), 5MB

Citation

Nozawa, K., Schneider, T. R., & Cramer, P. (2017). Core Mediator structure at 3.4 Å extends model of transcription initiation complex. Nature, 545(7653), 248-251. doi:10.1038/nature22328.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002D-2FCE-E
Abstract
Mediator is a multiprotein co-activator that binds the transcription pre-initiation complex (PIC) and regulates RNA polymerase (Pol) II. The Mediator head and middle modules form the essential core Mediator (cMed), whereas the tail and kinase modules play regulatory roles. The architecture of Mediator and its position on the PIC are known, but atomic details are limited to Mediator subcomplexes. Here we report the crystal structure of the 15-subunit cMed from Schizosaccharomyces pombe at 3.4 Å resolution. The structure shows an unaltered head module, and reveals the intricate middle module, which we show is globally required for transcription. Sites of known Mediator mutations cluster at the interface between the head and middle modules, and in terminal regions of the head subunits Med6 (ref. 16) and Med17 (ref. 17) that tether the middle module. The structure led to a model for Saccharomyces cerevisiae cMed that could be combined with the 3.6 Å cryo-electron microscopy structure of the core PIC (cPIC). The resulting atomic model of the cPIC-cMed complex informs on interactions of the submodules forming the middle module, called beam, knob, plank, connector, and hook. The hook is flexibly linked to Mediator by a conserved hinge and contacts the transcription initiation factor IIH (TFIIH) kinase that phosphorylates the carboxy (C)-terminal domain (CTD) of Pol II and was recently positioned on the PIC. The hook also contains residues that crosslink to the CTD and reside in a previously described cradle. These results provide a framework for understanding Mediator function, including its role in stimulating CTD phosphorylation by TFIIH.