Evolving Specificity from Variability for Protein Interaction Domains

Authors

Tomonori Kaneko, The University of Western Ontario
Sachdev S. Sidhu, University of Toronto
Shawn S. C. Li, The University of Western Ontario

Document Type

Article

Publication Date

4-2011

Journal

Trends in Biochemical Sciences

Volume

36

Issue

4

First Page

183

Last Page

190

URL with Digital Object Identifier

http://dx.doi.org/10.1016/j.tibs.2010.12.001

Abstract

An important question in modular domain-peptide interactions, which play crucial roles in many biological processes, is how the diverse specificities exhibited by different members of a domain family are encoded in a common scaffold. Analysis of the Src homology (SH) 2 family has revealed that its specificity is determined, in large part, by the configuration of surface loops that regulate ligand access to binding pockets. In a distinct manner, SH3 domains employ loops for ligand recognition. The PDZ domain, in contrast, achieves specificity by co-evolution of binding-site residues. Thus, the conformational and sequence variability afforded by surface loops and binding sites provides a general mechanism by which to encode the wide spectrum of specificities observed for modular protein interaction domains.