1gcq

From Proteopedia

Revision as of 09:21, 20 March 2008

CRYSTAL STRUCTURE OF VAV AND GRB2 SH3 DOMAINS

Overview

Vav is a guanine nucleotide exchange factor for the Rho/Rac family that is expressed exclusively in hematopoietic cells. Growth factor receptor-bound protein 2 (Grb2) has been proposed to play important roles in the membrane localization and activation of Vav through dimerization of its C-terminal Src-homology 3 (SH3) domain (GrbS) and the N-terminal SH3 domain of Vav (VavS). The crystal structure of VavS complexed with GrbS has been solved. VavS is distinct from other SH3 domain proteins in that its binding site for proline-rich peptides is blocked by its own RT loop. One of the ends of the VavS beta-barrel forms a concave hydrophobic surface. The GrbS components make a contiguous complementary interface with the VavS surface. The binding site of GrbS for VavS partially overlaps with the canonical binding site for proline-rich peptides, but is definitely different. Mutations at the interface caused a decrease in the binding affinity of VavS for GrbS by 4- to 40-fold. The structure reveals how GrbS discriminates VavS specifically from other signaling molecules without binding to the proline-rich motif.

Disease

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

About this Structure

1GCQ is a Protein complex structure of sequences from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA.

Reference

Novel recognition mode between Vav and Grb2 SH3 domains., Nishida M, Nagata K, Hachimori Y, Horiuchi M, Ogura K, Mandiyan V, Schlessinger J, Inagaki F, EMBO J. 2001 Jun 15;20(12):2995-3007. PMID:11406576

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