title: Protein-peptide interactions adopt the same structural motifs as monomeric protein folds.
abstract: We compared the modes of interaction between protein-peptide interfaces and those observed within monomeric proteins and found surprisingly few differences. Over 65% of 731 protein-peptide interfaces could be reconstructed within 1 A RMSD using solely fragment interactions occurring in monomeric proteins. Interestingly, more than 80% of interacting fragments used in reconstructing a protein-peptide binding site were obtained from monomeric proteins of an entirely different structural classification, with an average sequence identity below 15%. Nevertheless, geometric properties perfectly match the interaction patterns observed within monomeric proteins. We show the usefulness of our approach by redesigning the interaction scaffold of nine protein-peptide complexes, for which five of the peptides can be modeled within 1 A RMSD of the original peptide position. These data suggest that the wealth of structural data on monomeric proteins could be harvested to model protein-peptide interactions and, more importantly, that sequence homology is no prerequisite.
authors.affiliation: VIB SWITCH Laboratory, Brussels, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Vanhee
authors.forename: Francois
authors.initials: F
authors.lastname: Stricher
authors.forename: Lies
authors.initials: L
authors.lastname: Baeten
authors.forename: Erik
authors.initials: E
authors.lastname: Verschueren
authors.forename: Tom
authors.initials: T
authors.lastname: Lenaerts
authors.forename: Luis
authors.initials: L
authors.lastname: Serrano
authors.forename: Frederic
authors.initials: F
authors.lastname: Rousseau
authors.forename: Joost
authors.initials: J
authors.lastname: Schymkowitz
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D030562:Databases, Protein; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D017510:Protein Folding; D025941:Protein Interaction Mapping / Q000379:methods*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D010455:Peptides; D011506:Proteins