WW domain sequence activity relationships identified using ligand recognition propensities of 42 WW domains.
WW domains mediate protein-protein interactions in a number of different cellular functions by recognizing proline-containing peptide sequences. We determined peptide recognition propensities for 42 WW domains using NMR spectroscopy and peptide library screens. As potential ligands, we studied both model peptides and peptides based on naturally occurring sequences, including phosphorylated residues. Thirty-two WW domains were classified into six groups according to detected ligand recognition preferences for binding the motifs PPx(Y/poY), (p/phi)P(p,g)PPpR, (p/phi)PPRgpPp, PPLPp, (p/xi)PPPPP, and (poS/poT)P (motifs according to modified Seefeld Convention 2001). In addition to these distinct binding motifs, group-specific WW domain consensus sequences were identified. For PPxY-recognizing domains, phospho-tyrosine binding was also observed. Based on the sequences of the PPx(Y/poY)-specific group, a profile hidden Markov model was calculated and used to predict PPx(Y/poY)-recognition activity for WW domains, which were not assayed. PPx(Y/poY)-binding was found to be a common property of NEDD4-like ubiquitin ligases.
Otte
Livia
L
Institut für Medizinische Immunologie, Universitätsklinikum Charité, Schumannstr 20-21, 10117 Berlin, Germany.
Wiedemann
Urs
U
Schlegel
Brigitte
B
Pires
José Ricardo
JR
Beyermann
Michael
M
Schmieder
Peter
P
Krause
Gerd
G
Volkmer-Engert
Rudolf
R
Schneider-Mergener
Jens
J
Oschkinat
Hartmut
H
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D016384:Consensus Sequence; D004151:Dipeptides / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008390:Markov Chains; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D019151:Peptide Library; D019000:Phosphotyrosine; D011485:Protein Binding; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae; D017386:Sequence Homology, Amino Acid
D002352:Carrier Proteins; D004151:Dipeptides; D008024:Ligands; D010446:Peptide Fragments; D019151:Peptide Library; D019000:Phosphotyrosine