1R8S

ARF1[DELTA1-17]-GDP IN COMPLEX WITH A SEC7 DOMAIN CARRYING THE MUTATION OF THE CATALYTIC GLUTAMATE TO LYSINE

Summary for 1R8S

• Entry DOI: 10.2210/pdb1r8s/pdb
• Related: 1R8M 1R8Q 1R8R
• Descriptor: ADP-ribosylation factor 1, Arno, GUANOSINE-5'-DIPHOSPHATE, ... (8 entities in total)
• Functional Keywords: protein transport/exchange factor, protein transport-exchange factor complex
• Biological source: Bos taurus (cattle); More
• Cellular location: Golgi apparatus: P84080; Cell membrane ; Peripheral membrane protein : Q99418
• Total number of polymer chains: 2
• Total formula weight: 43096.69

Authors

Renault, L.,Guibert, B.,Cherfils, J. (deposition date: 2003-10-28, release date: 2004-01-20, Last modification date: 2023-08-23)

Primary citation

Renault, L.,Guibert, B.,Cherfils, J.
Structural snapshots of the mechanism and inhibition of a guanine nucleotide exchange factor
Nature, 426:525-530, 2003

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

Experimental method

X-RAY DIFFRACTION (1.46 Å)