3BJI

Structural Basis of Promiscuous Guanine Nucleotide Exchange by the T-Cell Essential Vav1

Summary for 3BJI

• Entry DOI: 10.2210/pdb3bji/pdb
• Related: 1F5X 1FOE
• Descriptor: Proto-oncogene vav, Ras-related C3 botulinum toxin substrate 1 precursor, ZINC ION, ... (4 entities in total)
• Functional Keywords: protein-protein interaction, gef/gtpase, atypical cysteine rich domain, guanine-nucleotide releasing factor, metal-binding, phorbol-ester binding, phosphoprotein, proto-oncogene, sh2 domain, sh3 domain, zinc, zinc-finger, adp-ribosylation, alternative splicing, gtp-binding, lipoprotein, membrane, methylation, nucleotide-binding, polymorphism, prenylation, signaling protein, structural genomics, psi-2, protein structure initiative, accelerated technologies center for gene to 3d structure, atcg3d
• Biological source: Homo sapiens (Human); More
• Cellular location: Cell membrane; Lipid-anchor; Cytoplasmic side (By similarity): P63000
• Total number of polymer chains: 4
• Total formula weight: 128661.33

Authors

Chrencik, J.E.,Brooun, A.,Kuhn, P.,Accelerated Technologies Center for Gene to 3D Structure (ATCG3D) (deposition date: 2007-12-04, release date: 2008-07-15, Last modification date: 2024-03-13)

Primary citation

Chrencik, J.E.,Brooun, A.,Zhang, H.,Mathews, I.I.,Hura, G.L.,Foster, S.A.,Perry, J.J.,Streiff, M.,Ramage, P.,Widmer, H.,Bokoch, G.M.,Tainer, J.A.,Weckbecker, G.,Kuhn, P.
Structural basis of guanine nucleotide exchange mediated by the T-cell essential Vav1.
J.Mol.Biol., 380:828-843, 2008

PubMed Abstract: The guanine nucleotide exchange factor (GEF) Vav1 plays an important role in T-cell activation and tumorigenesis. In the GEF superfamily, Vav1 has the ability to interact with multiple families of Rho GTPases. The structure of the Vav1 DH-PH-CRD/Rac1 complex to 2.6 A resolution reveals a unique intramolecular network of contacts between the Vav1 cysteine-rich domain (CRD) and the C-terminal helix of the Vav1 Dbl homology (DH) domain. These unique interactions stabilize the Vav1 DH domain for its intimate association with the Switch II region of Rac1 that is critical for the displacement of the guanine nucleotide. Small angle x-ray scattering (SAXS) studies support this domain arrangement for the complex in solution. Further, mutational analyses confirms that the atypical CRD is critical for maintaining both optimal guanine nucleotide exchange activity and broader specificity of Vav family GEFs. Taken together, the data outline the detailed nature of Vav1's ability to contact a range of Rho GTPases using a novel protein-protein interaction network.

PubMed: 18589439
DOI: 10.1016/j.jmb.2008.05.024

Experimental method

X-RAY DIFFRACTION (2.6 Å)