Publication Date:
2015-02-06
Description:
The conserved co-activator complex Mediator enables regulated transcription initiation by RNA polymerase (Pol) II. Here we reconstitute an active 15-subunit core Mediator (cMed) comprising all essential Mediator subunits from Saccharomyces cerevisiae. The cryo-electron microscopic structure of cMed bound to a core initiation complex was determined at 9.7 A resolution. cMed binds Pol II around the Rpb4-Rpb7 stalk near the carboxy-terminal domain (CTD). The Mediator head module binds the Pol II dock and the TFIIB ribbon and stabilizes the initiation complex. The Mediator middle module extends to the Pol II foot with a 'plank' that may influence polymerase conformation. The Mediator subunit Med14 forms a 'beam' between the head and middle modules and connects to the tail module that is predicted to bind transcription activators located on upstream DNA. The Mediator 'arm' and 'hook' domains contribute to a 'cradle' that may position the CTD and TFIIH kinase to stimulate Pol II phosphorylation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Plaschka, C -- Lariviere, L -- Wenzeck, L -- Seizl, M -- Hemann, M -- Tegunov, D -- Petrotchenko, E V -- Borchers, C H -- Baumeister, W -- Herzog, F -- Villa, E -- Cramer, P -- England -- Nature. 2015 Feb 19;518(7539):376-80. doi: 10.1038/nature14229. Epub 2015 Feb 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute for Biophysical Chemistry, Department of Molecular Biology, Am Fassberg 11, 37077 Gottingen, Germany. ; Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universitat Munchen, Feodor-Lynen-Strasse 25, 81377 Munich, Germany. ; Max Planck Institute for Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany. ; Department of Biochemistry and Microbiology, Genome British Columbia Protein Centre, University of Victoria, 3101-4464 Markham Street, Victoria, British Columbia V8Z7X8, Canada. ; 1] Max Planck Institute for Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany [2] Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25652824" target="_blank"〉PubMed〈/a〉
Keywords:
Allosteric Regulation
;
Binding Sites
;
*Cryoelectron Microscopy
;
DNA/chemistry/metabolism
;
Enzyme Activation
;
Mediator Complex/*chemistry/metabolism/*ultrastructure
;
Models, Molecular
;
Phosphorylation
;
Protein Stability
;
Protein Structure, Tertiary
;
Protein Subunits/chemistry/metabolism
;
RNA Polymerase II/*chemistry/metabolism/*ultrastructure
;
Saccharomyces cerevisiae/*chemistry/*ultrastructure
;
Saccharomyces cerevisiae Proteins/chemistry/metabolism/ultrastructure
;
Transcription Factor TFIIB/chemistry/metabolism
;
Transcription Factor TFIIH/chemistry/metabolism
;
Transcription Initiation, Genetic
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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