NUCLEAR-MAGNETIC-RESONANCE STRUCTURE OF AN SH2 DOMAIN OF PHOSPHOLIPASE C-GAMMA-1 COMPLEXED WITH A HIGH-AFFINITY BINDING PEPTIDE

The solution structure of the C-terminal SH2 domain of phospholipase C -gamma 1 (PLC-gamma 1), in complex with a phosphopeptide corresponding to its Tyr-1021 high affinity binding site on the platelet-derived gr owth factor receptor, has been determined by nuclear magnetic resonanc e spectroscopy. The topology of the SH2-phosphopeptide complex is simi lar to previously reported Src and Lck SH2 complexes. However, the bin ding site for residues C-terminal to the phosphotyrosine (pTyr) is an extended groove that contacts peptide residues at the +1 to +6 positio ns relative to the pTyr. This striking difference from Src and Lck ref lects the fact that the PLC-gamma 1 complex involves binding of a phos phopeptide with predominantly hydrophobic residues C-terminal to the p Tyr and therefore serves as a prototype for a second class of SH2-phos phopeptide interactions.