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1gfd

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Revision as of 09:22, 20 March 2008 by OCA (Talk | contribs)
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PDB ID 1gfd

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Gene: GRB2 (Homo sapiens)
Coordinates: save as pdb, mmCIF, xml



SOLUTION STRUCTURE AND LIGAND-BINDING SITE OF THE C-TERMINAL SH3 DOMAIN OF GRB2


Contents

Overview

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.

Disease

Known diseases associated with this structure: Central hypoventilation syndrome, congenital OMIM:[100790], Haddad syndrome OMIM:[100790]

About this Structure

1GFD is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

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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