1GCQ

CRYSTAL STRUCTURE OF VAV AND GRB2 SH3 DOMAINS

Summary for 1GCQ

• Entry DOI: 10.2210/pdb1gcq/pdb
• Related: 1GCP
• Descriptor: GROWTH FACTOR RECEPTOR-BOUND PROTEIN 2, VAV PROTO-ONCOGENE, (4R)-2-METHYLPENTANE-2,4-DIOL, ... (4 entities in total)
• Functional Keywords: sh3 domain, protein-protein complex, grb2, vav, signaling protein-signaling protein complex, signaling protein/signaling protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 22145.49

Authors

Nishida, M.,Nagata, K.,Hachimori, Y.,Ogura, K.,Inagaki, F. (deposition date: 2000-08-08, release date: 2001-08-08, Last modification date: 2023-12-27)

Primary citation

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

PubMed Abstract: 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.

PubMed: 11406576
DOI: 10.1093/emboj/20.12.2995

Experimental method

X-RAY DIFFRACTION (1.68 Å)