Detalle de: Conservation of coevolving protein interfaces bridges prokaryote–eukaryote homologies in the twilight zone

Significance Interacting proteins tend to coevolve through interdependent changes at the interaction interface. This phenomenon leads to patterns of coordinated mutations that can be exploited to systematically predict contacts between interacting proteins in prokaryotes. We explore the hypothesis that coevolving contacts at protein interfaces are preferentially conserved through long evolutionary periods. We demonstrate that coevolving residues in prokaryotes identify interprotein contacts that are particularly well conserved in the corresponding structure of their eukaryotic homologues. Therefore, these contacts have likely been important to maintain protein–protein interactions during evolution. We show that this property can be used to reliably predict interacting residues between eukaryotic proteins with homologues in prokaryotes even if they are very distantly related in sequence.