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1R8M

SEC7 DOMAIN OF THE ARF EXCHANGE FACTOR ARNO WITH BREFELDIN A-SENSITIZING MUTATIONS

Summary for 1R8M
Entry DOI10.2210/pdb1r8m/pdb
Related1BC9 1KU1 1PBV 1R8Q 1R8R 1R8S
DescriptorArno, MANGANESE (II) ION, FORMIC ACID, ... (4 entities in total)
Functional Keywordsexchange factor
Biological sourceHomo sapiens (human)
Cellular locationCell membrane ; Peripheral membrane protein : Q99418
Total number of polymer chains1
Total formula weight23615.72
Authors
Renault, L.,Guibert, B.,Cherfils, J. (deposition date: 2003-10-27, release date: 2004-01-20, Last modification date: 2024-10-30)
Primary citationRenault, L.,Guibert, B.,Cherfils, J.
Structural snapshots of the mechanism and inhibition of a guanine nucleotide exchange factor
Nature, 426:525-530, 2003
Cited by
PubMed Abstract: 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.
PubMed: 14654833
DOI: 10.1038/nature02197
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.7 Å)
Structure validation

226707

數據於2024-10-30公開中

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