title: A novel pro-Arg motif recognized by WW domains.
abstract: WW domains mediate protein-protein interactions through binding to short proline-rich sequences. Two distinct sequence motifs, PPXY and PPLP, are recognized by different classes of WW domains, and another class binds to phospho-Ser-Pro sequences. We now describe a novel Pro-Arg sequence motif recognized by a different class of WW domains using data from oriented peptide library screening, expression cloning, and in vitro binding experiments. The prototype member of this group is the WW domain of formin-binding protein 30 (FBP30), a p53-regulated molecule whose WW domains bind to Pro-Arg-rich cellular proteins. This new Pro-Arg sequence motif re-classifies the organization of WW domains based on ligand specificity, and the Pro-Arg class now includes the WW domains of FBP21 and FE65. A structural model is presented which rationalizes the distinct motifs selected by the WW domains of YAP, Pin1, and FBP30. The Pro-Arg motif identified for WW domains often overlaps with SH3 domain motifs within protein sequences, suggesting that the same extended proline-rich sequence could form discrete SH3 or WW domain complexes to transduce distinct cellular signals.
authors.affiliation: Department of Genetics, Harvard Medical School, Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Bedford
authors.forename: D
authors.initials: D
authors.lastname: Sarbassova
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: P
authors.initials: P
authors.lastname: Leder
authors.forename: M B
authors.initials: MB
authors.lastname: Yaffe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D004151:Dipeptides / Q000737:chemistry / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016716:PC12 Cells; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D019151:Peptide Library; D010768:Phosphoserine; D011487:Protein Conformation; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D018909:src Homology Domains
chemical_list: D002352:Carrier Proteins; D004151:Dipeptides; D050556:Fatty Acid-Binding Proteins; C106410:Fnbp1 protein, mouse; C402285:Fnbp4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D019151:Peptide Library; D011994:Recombinant Proteins; D010768:Phosphoserine; C045406:prolylarginine