FBP WW DOMAINS AND THE ABL SH3 DOMAIN BIND TO A SPECIFIC CLASS OF PROLINE-RICH LIGANDS

WW domains are conserved protein motifs of 38-40 amino acids found in a broad spectrum of proteins, They mediate protein-protein interaction s by binding proline-rich modules in ligands, A 10 amino acid proline- rich portion of the morphogenic protein, formin, is bound in vitro by both the WW domain of the formin-binding protein 11 (FBP11) and the SH 3 domain of Abl, To explore whether the FBP11 WW domain and Abl SH3 do main bind to similar ligands, we screened a mouse limb bud expression library for putative ligands of the FBP11 WW domain, In so doing, we i dentified eight ligands (WBP3 through WBP10), each of which contains a proline-rich region or regions, Peptide sequence comparisons of the l igands revealed a conserved motif of 10 amino acids that acts as a mod ular sequence binding the FBP11 WW domain, but not the WW domain of th e putative signal transducing factor, hYAP65. Interestingly, the conse nsus ligand for the FBP11 WW domain contains residues that are also re quired for binding by the Abl SH3 domain, These findings support the n otion that the FBP11 WW domain and the Abl SH3 domain can compete for the same proline-rich ligands and suggest that at least two subclasses of WW domains exist, namely those that bind a PPLP moth, and those th at bind a PPXY motif.