2024-03-29T09:33:07Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/78792022-10-13T09:03:45Zcom_20.500.12105_2174com_20.500.12105_2051com_20.500.12105_2173col_20.500.12105_2175
00925njm 22002777a 4500
dc
Rodriguez-Rivas, Juan
author
Marsili, Simone
author
Juan, David
author
Valencia, Alfonso
author
2016
Protein-protein interactions are fundamental for the proper functioning of the cell. As a result, protein interaction surfaces are subject to strong evolutionary constraints. Recent developments have shown that residue coevolution provides accurate predictions of heterodimeric protein interfaces from sequence information. So far these approaches have been limited to the analysis of families of prokaryotic complexes for which large multiple sequence alignments of homologous sequences can be compiled. We explore the hypothesis that coevolution points to structurally conserved contacts at protein-protein interfaces, which can be reliably projected to homologous complexes with distantly related sequences. We introduce a domain-centered protocol to study the interplay between residue coevolution and structural conservation of protein-protein interfaces. We show that sequence-based coevolutionary analysis systematically identifies residue contacts at prokaryotic interfaces that are structurally conserved at the interface of their eukaryotic counterparts. In turn, this allows the prediction of conserved contacts at eukaryotic protein-protein interfaces with high confidence using solely mutational patterns extracted from prokaryotic genomes. Even in the context of high divergence in sequence (the twilight zone), where standard homology modeling of protein complexes is unreliable, our approach provides sequence-based accurate information about specific details of protein interactions at the residue level. Selected examples of the application of prokaryotic coevolutionary analysis to the prediction of eukaryotic interfaces further illustrate the potential of this approach.
Proc Natl Acad Sci U S A. 2016;113(52):15018-15023
0027-8424
http://hdl.handle.net/20.500.12105/7879
27965389
10.1073/pnas.1611861114
1091-6490
Proceedings of the National Academy of Sciences of the United States of America
Coevolution
Contact prediction
Homology modeling
Protein complex
Protein–protein interaction
Conservation of coevolving protein interfaces bridges prokaryote-eukaryote homologies in the twilight zone