NMR structure of the N-terminal SH3 domain of GRB2 and its complex with a proline-rich peptide from Sos.
GRB2 is a small adaptor protein of 217 amino acids comprising one SH2 domain surrounded by two SH3 domains. GRB2 couples receptor tyrosine kinase activation to Ras signalling by interacting, through its SH3 domains, to the carboxy-terminal proline-rich regions of the guanine nucleotide exchange factor Sos. Here we report the synthesis and solution structure of the amino-terminal SH3 domain of GRB2 and of its more stable Ser 32 mutant. 1H NMR analysis of the complex between the Ser-32-GRB2-N-SH3 domain and the proline-rich peptide VPPPVPPRRR, derived from h-Sos, shows that relative to the SH3 peptide complexes described for PI3K, Fyn and Abl, the proline-rich peptide in this complex binds in the opposite orientation.
Goudreau
N
N
Département de Pharmacochimie-Moléculaire et Structurale, U266, INSERM-URA D1500 CNRS, Université René Descartes-UFR des Sciences Pharmaceutiques et Biologiques, Paris, France.
Cornille
F
F
Duchesne
M
M
Parker
F
F
Tocqué
B
B
Garbay
C
C
Roques
B P
BP
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D051380:GRB2 Adaptor Protein; D006801:Humans; D046911:Macromolecular Substances; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D010455:Peptides / Q000737:chemistry* / Q000235:genetics; D055232:Proline-Rich Protein Domains; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D012996:Solutions; D020664:Son of Sevenless Proteins
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D046911:Macromolecular Substances; D008565:Membrane Proteins; D010446:Peptide Fragments; D010455:Peptides; D011506:Proteins; D012996:Solutions; D020664:Son of Sevenless Proteins