Geranylgeranyl Switching Regulates
| Autor: | Wei Chen, Christelle Alory, Toshiaki Sakisaka, Jeanne Matteson, Ying Shao, Richard A. Gibbs, Ian A. Wilson, Yu An, William E. Balch |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
0303 health sciences
Chemistry C-terminus Allosteric regulation GDI prenylation GTPase Ligand (biochemistry) Rab vesicle transport Cell biology REP Vesicular transport protein 03 medical and health sciences 0302 clinical medicine Geranylgeranylation Biochemistry Prenylation Structural Biology Molecular Biology 030217 neurology & neurosurgery 030304 developmental biology |
| Zdroj: | Structure. 11(3):347-357 |
| ISSN: | 0969-2126 |
| DOI: | 10.1016/s0969-2126(03)00034-0 |
| Popis: | 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 (αGDI) 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 αGDI 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. |
| Databáze: | OpenAIRE |
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