title: Evolving specificity from variability for protein interaction domains.
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.
authors.affiliation: Department of Biochemistry and the Siebens-Drake Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, N6A 5C1, Canada.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Kaneko
authors.forename: Sachdev S
authors.initials: SS
authors.lastname: Sidhu
authors.forename: Shawn S C
authors.initials: SS
authors.lastname: Li
mesh_terms: D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D054730:Protein Interaction Domains and Motifs; D011506:Proteins / Q000737:chemistry*; D013379:Substrate Specificity
chemical_list: D008024:Ligands; D011506:Proteins