Sequence co-evolution gives 3D contacts and structures of protein complexes. Elife 2014 Sep 25;3
Date
09/26/2014Pubmed ID
25255213Pubmed Central ID
PMC4360534DOI
10.7554/eLife.03430Scopus ID
2-s2.0-84994885238 (requires institutional sign-in at Scopus site) 352 CitationsAbstract
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.
Author List
Hopf TA, Schärfe CP, Rodrigues JP, Green AG, Kohlbacher O, Sander C, Bonvin AM, Marks DSAuthor
David S. Marks MD Vice Chair, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Databases, ProteinEscherichia coli
Escherichia coli Proteins
Evolution, Molecular
Gene Expression
Gene Regulatory Networks
Genome, Bacterial
Models, Molecular
Protein Binding
Protein Conformation
Protein Interaction Mapping
