2VRW

Critical structural role for the PH and C1 domains of the Vav1 exchange factor

Summary for 2VRW

• Entry DOI: 10.2210/pdb2vrw/pdb
• Related: 1E96 1F5X 1FOE 1G4U 1GCP 1GCQ 1HE1 1HH4 1I4D 1I4L 1I4T 1K1Z 1MH1 1RYF 1RYH 2FJU
• Descriptor: RAS-RELATED C3 BOTULINUM TOXIN SUBSTRATE 1, PROTO-ONCOGENE VAV, ZINC ION, ... (4 entities in total)
• Functional Keywords: lipoprotein, gtp-binding, metal-binding, proto-oncogene, phosphoprotein, exchange factor, rac, vav, gtpase, membrane, sh2 domain, sh3 domain, methylation, zinc-finger, prenylation, guanine-nucleotide releasing factor, phorbol-ester binding, adp-ribosylation, nucleotide-binding, signaling protein
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Cell membrane; Lipid-anchor; Cytoplasmic side (By similarity): P63000
• Total number of polymer chains: 2
• Total formula weight: 68092.80

Authors

Rapley, J.,Tybulewicz, V.,Rittinger, K. (deposition date: 2008-04-16, release date: 2008-06-17, Last modification date: 2024-05-08)

Primary citation

Rapley, J.,Tybulewicz, V.,Rittinger, K.
Crucial Structural Role for the Ph and C1 Domains of the Vav1 Exchange Factor.
Embo Rep., 9:655-, 2008

PubMed Abstract: The Vav family of proteins are guanine nucleotide exchange factors (GEFs) for the Rho family of GTPases, which regulate various cellular functions, including T-cell activation. They contain a catalytic Dbl homology (DH) domain that is invariably followed by a pleckstrin homology (PH) domain, which is often required for catalytic activity. Vav proteins are the first GEFs for which an additional C1 domain is required for full biological activity. Here, we present the structure of a Vav1 fragment comprising the DH-PH-C1 domains bound to Rac1. This structure shows that the PH and C1 domains form a single structural unit that packs against the carboxy-terminal helix of the DH domain to stabilize its conformation and to promote nucleotide exchange. In contrast to previous reports, this structure shows that there are no direct contacts between the GTPase and C1 domain but instead suggests new mechanisms for the regulation of Vav1 activity.

PubMed: 18511940
DOI: 10.1038/EMBOR.2008.80

Experimental method

X-RAY DIFFRACTION (1.85 Å)