Conformation of an Shc-derived phosphotyrosine-containing peptide complexed with the Grb2 SH2 domain.
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.
Ogura
K
K
Department of Molecular Physiology, Tokyo Metropolitan Institute of Medical Science, Japan.
Tsuchiya
S
S
Terasawa
H
H
Yuzawa
S
S
Hatanaka
H
H
Mandiyan
V
V
Schlessinger
J
J
Inagaki
F
F
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
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; D010446:Peptide Fragments; D010748:Phosphopeptides; D011506:Proteins; D019000:Phosphotyrosine