1gfc
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SOLUTION STRUCTURE AND LIGAND-BINDING SITE OF THE C-TERMINAL SH3 DOMAIN OF GRB2
OverviewOverview
BACKGROUND: Growth factor receptor-bound protein 2 (GRB2) is an adaptor, protein with three Src homology (SH) domains in the order SH3-SH2-SH3., Both SH3 domains of GRB2 are necessary for interaction with the protein, Son of sevenless (Sos), which acts as a Ras activator. Thus, GRB2 mediates, signal transduction from growth factor receptors to Ras and is thought to, be a key molecule in signal transduction. RESULTS: The three-dimensional, structure of the carboxy-terminal SH3 domain of GRB2 (GRB2 C-SH3) was, determined by NMR spectroscopy. The SH3 structure consists of six, beta-strands arranged in two beta-sheets that are packed together, perpendicularly with two additional beta-strands forming the third, beta-sheet. GRB2 C-SH3 is very similar to SH3 domains from other proteins., The binding site of the ligand peptide (VPP-PVPPRRR) derived from the Sos, protein was mapped on the GRB2 C-SH3 domain indirectly using 1H and 15N, chemical shift changes, and directly using several intermolecular nuclear, Overhauser effects. CONCLUSIONS: Despite the structural similarity among, the known SH3 domains, the sequence alignment and the secondary structure, assignments differ. We therefore propose a standard description of the SH3, structures to facilitate comparison of individual SH3 domains, based on, their three-dimensional structures. The binding site of the ligand peptide, on GRB2 C-SH3 is in good agreement with those found in other SH3 domains.
DiseaseDisease
Known diseases associated with this structure: Central hypoventilation syndrome, congenital OMIM:[100790], Haddad syndrome OMIM:[100790]
About this StructureAbout this Structure
1GFC is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Solution structure and ligand-binding site of the carboxy-terminal SH3 domain of GRB2., Kohda D, Terasawa H, Ichikawa S, Ogura K, Hatanaka H, Mandiyan V, Ullrich A, Schlessinger J, Inagaki F, Structure. 1994 Nov 15;2(11):1029-40. PMID:7881903
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