Solution structure of the SH2 domain of Grb2 complexed with the Shc-derived phosphotyrosine-containing peptide.
The solution structure of growth factor receptor-bound protein 2 (Grb2) SH2 complexed with a Shc-derived phosphotyrosine (pTyr)-containing peptide was determined by nuclear magnetic resonance (NMR) spectroscopy. The pTyr binding site of Grb2 SH2 was similar to those of other SH2 domains. In contrast, the amino acid residues C-terminal to pTyr did not form an extended structure because of steric hindrance caused by a bulky side-chain of Trp121 (EF1). As a result, the peptide formed a turn-structure on the surface of Grb2 SH2. The asparagine residue at the pTyr+2 position of the Shc-peptide interacted with the main-chain carbonyl groups of Lys109 and Leu120. The present solution structure was similar to the crystal structure reported for Grb2 SH2 complexed with a BCR-Abl-derived phosphotyrosine-containing peptide. Finally, the structure of Grb2 SH2 domain was compared with those of the complexes of Src and phospholipase C-gamma1 with their cognate peptides, showing that the specific conformation of the peptide was required for binding to the SH2 domains.
Ogura
K
K
Department of Molecular Physiology, Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome Bunkyo-ku, Tokyo, 113, 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; D001665:Binding Sites; D066246:ErbB Receptors / Q000737:chemistry* / Q000378:metabolism; D051383:GRB10 Adaptor Protein; D051380:GRB2 Adaptor Protein; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D051966:Phospholipase C gamma; D019000:Phosphotyrosine / Q000737:chemistry; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D010738:Type C Phospholipases / Q000737:chemistry / Q000378:metabolism; D014633:Valine; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; D007527:Isoenzymes; D010446:Peptide Fragments; D011506:Proteins; D051383:GRB10 Adaptor Protein; D019000:Phosphotyrosine; D066246:ErbB Receptors; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D014633:Valine