Protein-peptide interactions adopt the same structural motifs as monomeric protein folds.
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.
Vanhee
Peter
P
VIB SWITCH Laboratory, Brussels, Belgium.
Stricher
Francois
F
Baeten
Lies
L
Verschueren
Erik
E
Lenaerts
Tom
T
Serrano
Luis
L
Rousseau
Frederic
F
Schymkowitz
Joost
J
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
D010455:Peptides; D011506:Proteins