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.
journal_name
EMBO Repjournal_title
EMBO reportsauthors
Rapley J,Tybulewicz VL,Rittinger Kdoi
10.1038/embor.2008.80subject
Has Abstractpub_date
2008-07-01 00:00:00pages
655-61issue
7eissn
1469-221Xissn
1469-3178pii
embor200880journal_volume
9pub_type
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