Publication Abstract from PubMed
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.
Geranylgeranyl switching regulates GDI-Rab GTPase recycling.,An Y, Shao Y, Alory C, Matteson J, Sakisaka T, Chen W, Gibbs RA, Wilson IA, Balch WE Structure. 2003 Mar;11(3):347-57. PMID:12623022[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
