Abstract
Rab/Ypt guanosine triphosphatases (GTPases) represent a family of key membrane traffic regulators in eukaryotic cells whose function is governed by the guanosine diphosphate (GDP) dissociation inhibitor (RabGDI). Using a combination of chemical synthesis and protein engineering, we generated and crystallized the monoprenylated Ypt1:RabGDI complex. The structure of the complex was solved to 1.5 angstrom resolution and provides a structural basis for the ability of RabGDI to inhibit the release of nucleotide by Rab proteins. Isoprenoid binding requires a conformational change that opens a cavity in the hydrophobic core of its domain II. Analysis of the structure provides a molecular basis for understanding a RabGDI mutant that causes mental retardation in humans.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites
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Crystallization
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Crystallography, X-Ray
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Guanine Nucleotide Dissociation Inhibitors / chemistry*
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Guanine Nucleotide Dissociation Inhibitors / genetics
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Guanine Nucleotide Dissociation Inhibitors / metabolism
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Guanosine Diphosphate / chemistry
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Guanosine Diphosphate / metabolism
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Hydrogen Bonding
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Hydrophobic and Hydrophilic Interactions
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Lipid Metabolism
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Magnesium / chemistry
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Magnesium / metabolism
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Models, Molecular
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Mutation
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Protein Binding
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Protein Conformation
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Protein Prenylation
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Saccharomyces cerevisiae Proteins / chemistry
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Saccharomyces cerevisiae Proteins / metabolism
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rab GTP-Binding Proteins / chemistry*
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rab GTP-Binding Proteins / metabolism
Substances
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GDP dissociation inhibitor 1
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Guanine Nucleotide Dissociation Inhibitors
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Recombinant Proteins
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Saccharomyces cerevisiae Proteins
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Guanosine Diphosphate
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YPT1 protein, S cerevisiae
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rab GTP-Binding Proteins
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Magnesium