title: Conformation of an Shc-derived phosphotyrosine-containing peptide complexed with the Grb2 SH2 domain.
abstract: We have determined the structure of an Shc-derived phosphotyrosine-containing peptide complexed with Grb2 SH2 based on intra- and intermolecular NOE correlations observed by a series of isotope-filtered NMR experiments using a PFG z-filter. In contrast to an extended conformation of phosphotyrosine-containing peptides bound to Src, Syp and PLC gamma SH2s, the Shc-derived peptide formed a turn at the +1 and +2 positions next to the phosphotyrosine residue. Trp121, located at the EF1 site of Grb2 SH2, blocked the peptide binding in an extended conformation. The present study confirms that each phosphotyrosine-containing peptide binds to the cognate SH2 with a specific conformation, which gives the structural basis for the binding specificity between SH2s and target proteins.
authors.affiliation: Department of Molecular Physiology, Tokyo Metropolitan Institute of Medical Science, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ogura
authors.forename: S
authors.initials: S
authors.lastname: Tsuchiya
authors.forename: H
authors.initials: H
authors.lastname: Terasawa
authors.forename: S
authors.initials: S
authors.lastname: Yuzawa
authors.forename: H
authors.initials: H
authors.lastname: Hatanaka
authors.forename: V
authors.initials: V
authors.lastname: Mandiyan
authors.forename: J
authors.initials: J
authors.lastname: Schlessinger
authors.forename: F
authors.initials: F
authors.lastname: Inagaki
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry; D010748:Phosphopeptides / Q000737:chemistry*; D019000:Phosphotyrosine; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; D010446:Peptide Fragments; D010748:Phosphopeptides; D011506:Proteins; D019000:Phosphotyrosine