title: Structure, function, and evolution of transient and obligate protein-protein interactions.
abstract: Recent analyses of high-throughput protein interaction data coupled with large-scale investigations of evolutionary properties of interaction networks have left some unanswered questions. To what extent do protein interactions act as constraints during evolution of the protein sequence? How does the type of interaction, specifically transient or obligate, play into these constraints? Are the mutations in the binding site of an interacting protein correlated with mutations in the binding site of its partner? We address these and other questions by relying on a carefully curated dataset of protein complex structures. Results point to the importance of distinguishing between transient and obligate interactions. We conclude that residues in the interfaces of obligate complexes tend to evolve at a relatively slower rate, allowing them to coevolve with their interacting partners. In contrast, the plasticity inherent in transient interactions leads to an increased rate of substitution for the interface residues and leaves little or no evidence of correlated mutations across the interface.
authors.affiliation: Bioinformatics Program and Biomedical Engineering Department, Boston University, Boston, MA 02215, USA.
authors.forename: Julian
authors.initials: J
authors.lastname: Mintseris
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Weng
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D019143:Evolution, Molecular; D006801:Humans; D008957:Models, Genetic; D046912:Multiprotein Complexes; D009154:Mutation; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D013997:Time Factors
chemical_list: D046912:Multiprotein Complexes; D011506:Proteins