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The multiple‐specificity landscape of modular peptide recognition domains

The multiple‐specificity landscape of modular peptide recognition domains

Authors :
David Gfeller
Frank Butty
Marta Wierzbicka
Erik Verschueren
Peter Vanhee
Haiming Huang
Andreas Ernst
Nisa Dar
Igor Stagljar
Luis Serrano
Sachdev S Sidhu
Gary D Bader
Philip M Kim
Source :
Molecular Systems Biology, Vol 7, Iss 1, Pp 1-12 (2011)
Publication Year :
2011
Publisher :
Springer Nature, 2011.

Abstract

Abstract Modular protein interaction domains form the building blocks of eukaryotic signaling pathways. Many of them, known as peptide recognition domains, mediate protein interactions by recognizing short, linear amino acid stretches on the surface of their cognate partners with high specificity. Residues in these stretches are usually assumed to contribute independently to binding, which has led to a simplified understanding of protein interactions. Conversely, we observe in large binding peptide data sets that different residue positions display highly significant correlations for many domains in three distinct families (PDZ, SH3 and WW). These correlation patterns reveal a widespread occurrence of multiple binding specificities and give novel structural insights into protein interactions. For example, we predict a new binding mode of PDZ domains and structurally rationalize it for DLG1 PDZ1. We show that multiple specificity more accurately predicts protein interactions and experimentally validate some of the predictions for the human proteins DLG1 and SCRIB. Overall, our results reveal a rich specificity landscape in peptide recognition domains, suggesting new ways of encoding specificity in protein interaction networks.

Details

Language :
English
ISSN :
17444292
Volume :
7
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Molecular Systems Biology
Publication Type :
Academic Journal
Accession number :
edsdoj.58aa78edee014b94bebe4bf7b70588db
Document Type :
article
Full Text :
https://doi.org/10.1038/msb.2011.18