title: Evolvability of yeast protein-protein interaction interfaces.
abstract: The functional importance of protein-protein interactions indicates that there should be strong evolutionary constraint on their interaction interfaces. However, binding interfaces are frequently affected by amino acid replacements. Change due to coevolution within interfaces can contribute to variability but is not ubiquitous. An alternative explanation for the ability of surfaces to accept replacements may be that many residues can be changed without affecting the interaction. Candidates for these types of residues are those that make interchain interaction only through the protein main chain, β-carbon, or associated hydrogen atoms. Since almost all residues have these atoms, we hypothesize that this subset of interface residues may be more easily substituted than those that make interactions through other atoms. We term such interactions "residue type independent." Investigating this hypothesis, we find that nearly a quarter of residues in protein interaction interfaces make exclusively interchain residue-type-independent contacts. These residues are less structurally constrained and less conserved than residues making residue-type-specific interactions. We propose that residue-type-independent interactions allow substitutions in binding interfaces while the specificity of binding is maintained.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
authors.forename: David
authors.initials: D
authors.lastname: Talavera
authors.forename: Simon G
authors.initials: SG
authors.lastname: Williams
authors.forename: Matthew G S
authors.initials: MG
authors.lastname: Norris
authors.forename: David L
authors.initials: DL
authors.lastname: Robertson
authors.forename: Simon C
authors.initials: SC
authors.lastname: Lovell
mesh_terms: D030562:Databases, Protein; D019143:Evolution, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics
chemical_list: D029701:Saccharomyces cerevisiae Proteins