title: Can we infer peptide recognition specificity mediated by SH3 domains?
abstract: Protein interaction domain families that modulate the formation of macromolecular complexes recognize specific sequence or structural motifs. For instance SH3 and WW domains bind to polyproline peptides while SH2 and FHA domains bind to peptides phosphorylated in Tyr and Thr respectively. Within each family, variations in the chemical characteristics of the domain binding pocket modulate a finer peptide recognition specificity and, as a consequence, determine the selection of functional protein partners in vivo. In the proteomic era there is the need for reliable inference methods to help restricting the sequence space of the putative targets to be confirmed experimentally by more laborious experimental approaches. Here we will review the published data about the peptide recognition specificity of the SH3 domain family and we will propose a classification of SH3 domains into eight classes. Finally, we will discuss whether the available information is sufficient to infer the recognition specificity of any uncharacterized SH3 domain.
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 00133 Rome, Italy. giovanni.cesareni@uniroma2.it
authors.forename: Gianni
authors.initials: G
authors.lastname: Cesareni
authors.forename: Simona
authors.initials: S
authors.lastname: Panni
authors.forename: Giuliano
authors.initials: G
authors.lastname: Nardelli
authors.forename: Luisa
authors.initials: L
authors.lastname: Castagnoli
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D016384:Consensus Sequence; D010455:Peptides / Q000737:chemistry*; D010769:Phosphothreonine; D019000:Phosphotyrosine; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D018909:src Homology Domains
chemical_list: D010455:Peptides; D011506:Proteins; D010769:Phosphothreonine; D019000:Phosphotyrosine