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 growth factor receptor, has been determined by nuclear magnetic resonance spectroscopy. The topology of the SH2-phosphopeptide complex is similar to previously reported Src and Lck SH2 complexes. However, the binding site for residues C-terminal to the phosphotyrosine (pTyr) is an extended groove that contacts peptide residues at the +1 to +6 positions relative to the pTyr. This striking difference from Src and Lck reflects the fact that the PLC-gamma 1 complex involves binding of a phosphopeptide with predominantly hydrophobic residues C-terminal to the pTyr and therefore serves as a prototype for a second class of SH2-phosphopeptide interactions.
Pascal
S M
SM
Biochemistry Research Division, Hospital for Sick Children, Toronto, Ontario, Canada.
Singer
A U
AU
Gish
G
G
Yamazaki
T
T
Shoelson
S E
SE
Pawson
T
T
Kay
L E
LE
Forman-Kay
J D
JD
D000595:Amino Acid Sequence; D001665:Binding Sites; D007527:Isoenzymes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D051966:Phospholipase C gamma; D010748:Phosphopeptides / Q000138:chemical synthesis / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017479:Receptors, Platelet-Derived Growth Factor / Q000737:chemistry; D016415:Sequence Alignment; D010738:Type C Phospholipases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D007527:Isoenzymes; D010748:Phosphopeptides; D017479:Receptors, Platelet-Derived Growth Factor; D010738:Type C Phospholipases; D051966:Phospholipase C gamma