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

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Cite this article as: eLife 2014;3:e03430 doi: 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

Thomas A Hopf

Harvard University, Boston, United States

Competing interests
The authors declare that no competing interests exist.
Charlotta P.I Schärfe

University of Tübingen, Tübingen, Germany

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The authors declare that no competing interests exist.
João P.G.L.M Rodrigues

Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, Netherlands

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The authors declare that no competing interests exist.
Anna G Green

Harvard Medical School, Boston, United States

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The authors declare that no competing interests exist.
Oliver Kohlbacher

University of Tübingen, Tübingen, Germany

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The authors declare that no competing interests exist.
Chris Sander

Memorial Sloan Kettering Cancer Center, New York, United States

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The authors declare that no competing interests exist.
Alexandre M.J.J. Bonvin

Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, Netherlands

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The authors declare that no competing interests exist.
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

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

Publication history

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

Copyright

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.