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Cell. 1998 Oct 16;95(2):237-48.

Structural basis for activation of ARF GTPase: mechanisms of guanine nucleotide exchange and GTP-myristoyl switching.

Author information

1
Cellular Biochemistry and Biophysics Program Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. jonathan@ximpact4.ski.mskcc.org

Abstract

Ras-related GTPases are positively regulated by guanine nucleotide exchange factors (GEFs) that promote the exchange of GDP for GTP. The crystal structure of the Sec7 domain GEF bound to nucleotide-free ARF1 GTPase has been determined at 2.8 A resolution and the structure of ARF1 in the GTP-analog form determined at 1.6 A resolution. The Sec7 domain binds to the switch regions of ARF1 and inserts residues directly into the GTPase active site. The interaction leaves the purine-binding site intact but perturbs the Mg2+ and phosphate groups to promote the dissociation of guanine nucleotides. The structure of ARF1 in the GTP-analog form closely resembles Ras, revealing a substantial rearrangement from the GDP conformation. The transition controls the exposure of the myristoylated N terminus, explaining how ARF GTPases couple the GDP-GTP conformational switch to membrane binding.

PMID:
9790530
DOI:
10.1016/s0092-8674(00)81754-7
[Indexed for MEDLINE]
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