Structure of the N-terminal SH3 domain of GRB2 complexed with a peptide from the guanine nucleotide releasing factor Sos.
Src-homology 3 (SH3) domains mediate signal transduction by binding to proline-rich motifs in target proteins. We have determined the high-resolution NMR structure of the complex between the amino-terminal SH3 domain of GRB2 and a ten amino acid peptide derived from the guanine nucleotide releasing factor Sos. The NMR data show that the peptide adopts the conformation of a left-handed polyproline type II helix and interacts with three major sites on the SH3 domain. The orientation of the bound peptide is opposite to that of proline-rich peptides bound to the SH3 domains of Abl, Fyn and p85.
Terasawa
H
H
Department of Molecular Physiology, Tokyo Metropolitan Institute of Medical Science, Japan.
Kohda
D
D
Hatanaka
H
H
Tsuchiya
S
S
Ogura
K
K
Nagata
K
K
Ishii
S
S
Mandiyan
V
V
Ullrich
A
A
Schlessinger
J
J
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D051380:GRB2 Adaptor Protein; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D010455:Peptides / Q000737:chemistry / Q000235:genetics; D055232:Proline-Rich Protein Domains; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D020664:Son of Sevenless Proteins
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; D008024:Ligands; D008565:Membrane Proteins; D010446:Peptide Fragments; D010455:Peptides; D011506:Proteins; D020664:Son of Sevenless Proteins