2EFH

Ara7-GDP/AtVps9a(D185N)

Summary for 2EFH

• Entry DOI: 10.2210/pdb2efh/pdb
• Related: 2efd 2efe 2fec
• Descriptor: Similarity to vacuolar protein sorting-associated protein VPS9, Small GTP-binding protein-like, GUANOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: gef, gtpase, vps9, rab5, nucleotide, transport protein
• Biological source: Arabidopsis thaliana (thale cress); More
• Cellular location: Early endosome membrane: Q9SN68
• Total number of polymer chains: 4
• Total formula weight: 100995.93

Authors

Ihara, K.,Uejima, T.,Wakatsuki, S. (deposition date: 2007-02-22, release date: 2008-02-26, Last modification date: 2024-04-03)

Primary citation

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., 285:36689-36697, 2010

PubMed Abstract: 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 β-phosphate directly and pulls the P-loop lysine of ARA7 away from GDP β-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.

PubMed: 20833725
DOI: 10.1074/jbc.M110.152132

Experimental method

X-RAY DIFFRACTION (2.1 Å)