Mapping the Specificity of SH3 Domains with Phage-Displayed Random-Peptide Libraries

Recent inqui-res into the molecular mechanisms underlying cellular behavior have underscored the importance of dynamic associations between proteins, or protein-protein interactions, in regulating a variety of brological processes. These protein-protein interactions are often mediated by conserved-modular domains, such as the Src Homology domains 2 and 3, known as SH2 and SH3 (1 ,2 ). Recently, combmatorral-peptrde libraries have been used to define high-affinity peptide ligands for a variety of modular domains (3 –8 ). Ligands derived from these libraries often resemble sequences in natural-binding proteins. Thus, combinatorral-peptide libraries provide a means of mapping modular domain-mediated protein-protein interactions, particularly where the natural target of the domain is a short linear stretch of ammo acids.