1r8q
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FULL-LENGTH ARF1-GDP-MG IN COMPLEX WITH BREFELDIN A AND A SEC7 DOMAIN
OverviewOverview
Small GTP-binding (G) proteins are activated by GDP/GTP nucleotide, exchange stimulated by guanine nucleotide exchange factors (GEFs)., Nucleotide dissociation from small G protein-GEF complexes involves, transient GDP-bound intermediates whose structures have never been, described. In the case of Arf proteins, small G proteins that regulate, membrane traffic in eukaryotic cells, such intermediates can be trapped, either by the natural inhibitor brefeldin A or by charge reversal at the, catalytic glutamate of the Sec7 domain of their GEFs. Here we report the, crystal structures of these intermediates that show that membrane, recruitment of Arf and nucleotide dissociation are separate reactions, stimulated by Sec7. The reactions proceed through sequential rotations of, the Arf.GDP core towards the Sec7 catalytic site, and are blocked by, interfacial binding of brefeldin A and unproductive stabilization of GDP, by charge reversal. The structural characteristics of the reaction and its, modes of inhibition reveal unexplored ways in which to inhibit the, activation of small G proteins.
About this StructureAbout this Structure
1R8Q is a Protein complex structure of sequences from Bos taurus and Homo sapiens with MG, ZN, G3D and AFB as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Structural snapshots of the mechanism and inhibition of a guanine nucleotide exchange factor., Renault L, Guibert B, Cherfils J, Nature. 2003 Dec 4;426(6966):525-30. PMID:14654833
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