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

Cell. 1998 Oct 16;95(2):237-48. doi: 10.1016/s0092-8674(00)81754-7.

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.

MeSH terms

  • ADP-Ribosylation Factor 1
  • ADP-Ribosylation Factors
  • Binding Sites / physiology
  • Crystallography
  • Fungal Proteins / chemistry
  • Fungal Proteins / metabolism
  • GTP Phosphohydrolases / chemistry*
  • GTP Phosphohydrolases / metabolism
  • GTP-Binding Proteins / chemistry*
  • GTP-Binding Proteins / metabolism*
  • Guanine Nucleotide Exchange Factors*
  • Guanosine Triphosphate / metabolism*
  • Molecular Sequence Data
  • Myristic Acid / metabolism*
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Yeasts / chemistry
  • Yeasts / metabolism

Substances

  • Fungal Proteins
  • Guanine Nucleotide Exchange Factors
  • Sec7 guanine nucleotide exchange factors
  • Myristic Acid
  • Guanosine Triphosphate
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • ADP-Ribosylation Factor 1
  • ADP-Ribosylation Factors

Associated data

  • PDB/UNKNOWN