Send to

Choose Destination
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

Cellular Biochemistry and Biophysics Program Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.


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.

[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center