| Structural highlights
Function
[VPS9A_ARATH] Functions as guanine nucleotide exchange factor (GEF) for Rab small GTPases. Activates specifically RABF1, RABF2A and RABF2B proteins. Required for early stages of embryogenesis, cytokinesis, embryogenesis, and organ development. Is essential for the establishment or maintenance of the polar localization of the auxin efflux carrier PIN1.[1] [2] [RAF2B_ARATH] Endosomal protein that may be involved in endocytosis.[3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Many GTPases regulate intracellular transport and signaling in eukaryotes. Guanine nucleotide exchange factors (GEFs) activate GTPases by catalyzing the exchange of their GDP for GTP. Here we present crystallographic and biochemical studies of a GEF reaction with four crystal structures of Arabidopsis thaliana ARA7, a plant homolog of Rab5 GTPase, in complex with its GEF, VPS9a, in the nucleotide-free and GDP-bound forms, as well as a complex with aminophosphonic acid-guanylate ester and ARA7.VPS9a(D185N) with GDP. Upon complex formation with ARA7, VPS9 wedges into the interswitch region of ARA7, inhibiting the coordination of Mg(2+) and decreasing the stability of GDP binding. The aspartate finger of VPS9a recognizes GDP beta-phosphate directly and pulls the P-loop lysine of ARA7 away from GDP beta-phosphate toward switch II to further destabilize GDP for its release during the transition from the GDP-bound to nucleotide-free intermediates in the nucleotide exchange reaction.
GDP-bound and nucleotide-free intermediates of the guanine nucleotide exchange in the Rab5.Vps9 system.,Uejima T, Ihara K, Goh T, Ito E, Sunada M, Ueda T, Nakano A, Wakatsuki S J Biol Chem. 2010 Nov 19;285(47):36689-97. Epub 2010 Sep 10. PMID:20833725[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Goh T, Uchida W, Arakawa S, Ito E, Dainobu T, Ebine K, Takeuchi M, Sato K, Ueda T, Nakano A. VPS9a, the common activator for two distinct types of Rab5 GTPases, is essential for the development of Arabidopsis thaliana. Plant Cell. 2007 Nov;19(11):3504-15. Epub 2007 Nov 30. PMID:18055610 doi:10.1105/tpc.107.053876
- ↑ Uejima T, Ihara K, Goh T, Ito E, Sunada M, Ueda T, Nakano A, Wakatsuki S. GDP-bound and nucleotide-free intermediates of the guanine nucleotide exchange in the Rab5.Vps9 system. J Biol Chem. 2010 Nov 19;285(47):36689-97. Epub 2010 Sep 10. PMID:20833725 doi:10.1074/jbc.M110.152132
- ↑ Uejima T, Ihara K, Goh T, Ito E, Sunada M, Ueda T, Nakano A, Wakatsuki S. GDP-bound and nucleotide-free intermediates of the guanine nucleotide exchange in the Rab5.Vps9 system. J Biol Chem. 2010 Nov 19;285(47):36689-97. Epub 2010 Sep 10. PMID:20833725 doi:10.1074/jbc.M110.152132
- ↑ Uejima T, Ihara K, Goh T, Ito E, Sunada M, Ueda T, Nakano A, Wakatsuki S. GDP-bound and nucleotide-free intermediates of the guanine nucleotide exchange in the Rab5.Vps9 system. J Biol Chem. 2010 Nov 19;285(47):36689-97. Epub 2010 Sep 10. PMID:20833725 doi:10.1074/jbc.M110.152132
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