title: Architecture of the RNA polymerase II-Mediator core initiation complex.
abstract: 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 Å 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.
authors: Max Planck Institute for Biophysical Chemistry, Department of Molecular Biology, Am Fassberg 11, 37077 Göttingen, Germany.
authors: C
authors: C
authors: Plaschka
authors: Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.
authors: L
authors: L
authors: Larivière
authors: Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.
authors: L
authors: L
authors: Wenzeck
authors: Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.
authors: M
authors: M
authors: Seizl
authors: Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.
authors: M
authors: M
authors: Hemann
authors: Max Planck Institute for Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors: D
authors: D
authors: Tegunov
authors: Department of Biochemistry and Microbiology, Genome British Columbia Protein Centre, University of Victoria, 3101-4464 Markham Street, Victoria, British Columbia V8Z7X8, Canada.
authors: E V
authors: EV
authors: Petrotchenko
authors: Department of Biochemistry and Microbiology, Genome British Columbia Protein Centre, University of Victoria, 3101-4464 Markham Street, Victoria, British Columbia V8Z7X8, Canada.
authors: C H
authors: CH
authors: Borchers
authors: Max Planck Institute for Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors: W
authors: W
authors: Baumeister
authors: Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.
authors: F
authors: F
authors: Herzog
authors: 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.
authors: E
authors: E
authors: Villa
authors: Max Planck Institute for Biophysical Chemistry, Department of Molecular Biology, Am Fassberg 11, 37077 Göttingen, Germany.
authors: P
authors: P
authors: Cramer
mesh_terms: D000494:Allosteric Regulation; D001665:Binding Sites; D020285:Cryoelectron Microscopy; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004789:Enzyme Activation; D056892:Mediator Complex / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure*; D008958:Models, Molecular; D010766:Phosphorylation; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D012319:RNA Polymerase II / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure*; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000648:ultrastructure*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D035581:Transcription Factor TFIIB / Q000737:chemistry / Q000378:metabolism; D051758:Transcription Factor TFIIH / Q000737:chemistry / Q000378:metabolism; D061785:Transcription Initiation, Genetic
chemical_list: D056892:Mediator Complex; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D035581:Transcription Factor TFIIB; D051758:Transcription Factor TFIIH; D004247:DNA; D012319:RNA Polymerase II; C423309:RPB4 protein, S cerevisiae; C470553:RPB7 protein, S cerevisiae
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