1. Structural Biology and Molecular Biophysics
Download icon

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
Research Article
  • Cited 195
  • Views 12,792
  • Annotations
Cite this article as: eLife 2014;3:e03430 doi: 10.7554/eLife.03430

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.

Article and author information

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

Publication 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.

Metrics

  • 12,792
    Page views
  • 1,960
    Downloads
  • 195
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics
    James Chen et al.
    Research Article Updated
    1. Cell Biology
    2. Structural Biology and Molecular Biophysics
    Tatyana Bodrug et al.
    Research Article