Biochemistry Publications

Title

Evolving Specificity from Variability for Protein Interaction Domains

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.