1. Structural Biology and Molecular Biophysics
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Molecular architecture of the yeast Mediator complex

  1. Philip J Robinson
  2. Michael J Trnka
  3. Riccardo Pellarin
  4. Charles H Greenberg
  5. David A Bushnell
  6. Ralph Davis
  7. Alma L Burlingame
  8. Andrej Sali
  9. Roger D Kornberg  Is a corresponding author
  1. Stanford University School of Medicine, United States
  2. University of California, San Francisco, United States
Research Article
  • Cited 84
  • Views 5,650
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Cite this article as: eLife 2015;4:e08719 doi: 10.7554/eLife.08719

Abstract

The 21-subunit Mediator complex transduces regulatory information from enhancers to promoters, and performs an essential role in the initiation of transcription in all eukaryotes. Structural information on two-thirds of the complex has been limited to coarse subunit mapping onto 2-D images from electron micrographs. We have performed chemical cross-linking and mass spectrometry, and combined the results with information from X-ray crystallography, homology modeling, and cryo-electron microscopy by an integrative modeling approach to determine a 3-D model of the entire Mediator complex. The approach is validated by the use of X-ray crystal structures as internal controls and by consistency with previous results from electron microscopy and yeast two-hybrid screens. The model shows the locations and orientations of all Mediator subunits, as well as subunit interfaces and some secondary structural elements. Segments of 20-40 amino acid residues are placed with an average precision of 20 Å. The model reveals roles of individual subunits in the organization of the complex.

Article and author information

Author details

  1. Philip J Robinson

    Department of Structural Biology, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Michael J Trnka

    Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Riccardo Pellarin

    Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Charles H Greenberg

    Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. David A Bushnell

    Department of Structural Biology, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Ralph Davis

    Department of Structural Biology, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Alma L Burlingame

    Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Andrej Sali

    Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Roger D Kornberg

    Department of Structural Biology, Stanford University School of Medicine, Stanford, United States
    For correspondence
    kornberg@stanford.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Irwin Davidson, Institut de Génétique et de Biologie Moléculaire et Cellulaire, France

Publication history

  1. Received: May 14, 2015
  2. Accepted: September 23, 2015
  3. Accepted Manuscript published: September 24, 2015 (version 1)
  4. Version of Record published: November 4, 2015 (version 2)

Copyright

© 2015, Robinson et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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