1. Structural Biology and Molecular Biophysics

Sequence co-evolution gives 3D contacts and structures of protein complexes

  1. Thomas A Hopf
  2. Charlotta P.I Schärfe
  3. João P.G.L.M Rodrigues
  4. Anna G Green
  5. Oliver Kohlbacher
  6. Chris Sander
  7. Alexandre M.J.J. Bonvin
  8. Debora S Marks  Is a corresponding author
  1. Harvard University, United States
  2. University of Tübingen, Germany
  3. Bijvoet Center for Biomolecular Research, Utrecht University, Netherlands
  4. Harvard Medical School, United States
  5. Memorial Sloan Kettering Cancer Center, United States
https://doi.org/10.7554/eLife.03430
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  1. Thomas A Hopf
  2. Charlotta P.I Schärfe
  3. João P.G.L.M Rodrigues
  4. Anna G Green
  5. Oliver Kohlbacher
  6. Chris Sander
  7. Alexandre M.J.J. Bonvin
  8. Debora S Marks
(2014)
Sequence co-evolution gives 3D contacts and structures of protein complexes
eLife 3:e03430.
https://doi.org/10.7554/eLife.03430
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Abstract

Protein-protein interactions are fundamental to many biological processes. Experimental screens have identified tens of thousands of interactions and structural biology has provided detailed functional insight for select 3D protein complexes. An alternative rich source of information about protein interactions is the evolutionary sequence record. Building on earlier work, we show that analysis of correlated evolutionary sequence changes across proteins identifies residues that are close in space with sufficient accuracy to determine the three-dimensional structure of the protein complexes. We evaluate prediction performance in blinded tests on 76 complexes of known 3D structure, predict protein-protein contacts in 32 complexes of unknown structure, and demonstrate how evolutionary couplings can be used to distinguish between interacting and non-interacting protein pairs in a large complex. With the current growth of sequences, we expect that the method can be generalized to genome-wide elucidation of protein-protein interaction networks and used for interaction predictions at residue resolution.

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Author details

  1. Thomas A Hopf

    Harvard University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Charlotta P.I Schärfe

    University of Tübingen, Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.

  3. João P.G.L.M Rodrigues

    Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

  4. Anna G Green

    Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Oliver Kohlbacher

    University of Tübingen, Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.

  6. Chris Sander

    Memorial Sloan Kettering Cancer Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Alexandre M.J.J. Bonvin

    Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

  8. Debora S Marks

    Harvard University, Boston, United States
    For correspondence
    debbie@hms.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. John Kuriyan, Howard Hughes Medical Institute, University of California, Berkeley, United States

Version history

  1. Received: May 21, 2014
  2. Accepted: September 23, 2014
  3. Accepted Manuscript published: September 25, 2014 (version 1)
  4. Version of Record published: November 3, 2014 (version 2)

Copyright

© 2014, Hopf 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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  1. Thomas A Hopf
  2. Charlotta P.I Schärfe
  3. João P.G.L.M Rodrigues
  4. Anna G Green
  5. Oliver Kohlbacher
  6. Chris Sander
  7. Alexandre M.J.J. Bonvin
  8. Debora S Marks
(2014)
Sequence co-evolution gives 3D contacts and structures of protein complexes
eLife 3:e03430.
https://doi.org/10.7554/eLife.03430

Share this article

https://doi.org/10.7554/eLife.03430

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