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

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 sequence databases, 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.

• Publication year

  2014

• Venue

  bioRxiv

• Publication date

  2014-05-05

• Fields of study

  Biology, Medicine, Chemistry, Computer Science

• Identifiers
  DOI 10.7554/eLife.03430arXiv 1405.0929PMID 25255213PMCID 4360534
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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