title: Probing WW Domains to Uncover and Refine Determinants of Specificity in Ligand Recognition.
abstract: Understanding the specificity of protein-protein interaction mediated by domains and their ligands will have strong impact on basic and applied research. Visual inspection of WW domain sequences prompted a general classification of the domains into two large subfamilies. One subfamily contains two consecutive aromatic residues in the beta 2 strand of the domain whereas the other contains three or four consecutive aromatic residues in the same position. In the recent past, we proposed a rule of 'two vs. three aromatics' in the beta 2 strand of WW domains as a molecular discriminator between Class I and Class II WW domains, which recognize PPxY or PPLP motifs, respectively. Using phage display libraries expressing WW domains with random sequences replacing a part of the beta 2 strand, we provided additional evidence supporting our rule. We conclude that three consecutive aromatic amino acids within the beta 2 strand of WW domain are required but not always sufficient for the WW domain to belong to Class II.
authors.affiliation: Sanofi-Synthelabo, Labege Innopole Voie 1, 31676, Labege, France.
authors.forename: X
authors.initials: X
authors.lastname: Espanel
authors.forename: N
authors.initials: N
authors.lastname: Navin
authors.forename: Y
authors.initials: Y
authors.lastname: Kato
authors.forename: M
authors.initials: M
authors.lastname: Tanokura
authors.forename: M
authors.initials: M
authors.lastname: Sudol