Geranylgeranyl switching regulates GDI-Rab GTPase recycling

Structure. 2003 Mar;11(3):347-57. doi: 10.1016/s0969-2126(03)00034-0.


Rab GTPases, key regulators of membrane targeting and fusion, require the covalent attachment of geranylgeranyl lipids to their C terminus for function. To elucidate the role of lipid in Rab recycling, we have determined the crystal structure of Rab guanine nucleotide dissociation inhibitor (alphaGDI) in complex with a geranylgeranyl (GG) ligand (H(2)N-Cys-(S-GG)-OMe). The lipid is bound beneath the Rab binding platform in a shallow hydrophobic groove. Mutation of the binding pocket in the brain-specific alphaGDI leads to mental retardation. Strikingly, lipid binding acts through a conserved allosteric switching mechanism to promote release of the GDI-Rab[GDP] complex from the membrane.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Diterpenes / metabolism*
  • GTP Phosphohydrolases / metabolism*
  • Guanine Nucleotide Dissociation Inhibitors / metabolism*
  • Leucine / metabolism
  • Ligands
  • Lipid Metabolism
  • Phenylalanine / metabolism


  • Diterpenes
  • GDP dissociation inhibitor 1
  • Guanine Nucleotide Dissociation Inhibitors
  • Ligands
  • Phenylalanine
  • geranylgeranic acid
  • GTP Phosphohydrolases
  • Leucine

Associated data

  • PDB/1LV0