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 Å RMSD using solely fragment interactions occurring in monomeric pro...

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Bibliographic Details
Published in:Structure (London) 2009-08, Vol.17 (8), p.1128-1136
Main Authors: Vanhee, Peter, Stricher, Francois, Baeten, Lies, Verschueren, Erik, Lenaerts, Tom, Serrano, Luis, Rousseau, Frederic, Schymkowitz, Joost
Format: Article
Language:English
Subjects:
Algorithms
Binding Sites
Databases, Protein
Models, Molecular
Peptides - chemistry
Protein Binding
Protein Folding
Protein Interaction Mapping - methods
Protein Structure, Secondary
Protein Structure, Tertiary
PROTEINS
Proteins - chemistry
Structure-Activity Relationship
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Summary: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 Å 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 Å 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.
ISSN:0969-2126
1878-4186
DOI:10.1016/j.str.2009.06.013