Structure of Rab GDP-dissociation inhibitor in complex with prenylated YPT1 GTPase.

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.

• Authors: Alexey Rak, Olena Pylypenko, Thomas Durek, Anja Watzke, Susanna Kushnir, Lucas Brunsveld, Herbert Waldmann, Roger S Goody, Kirill Alexandrov
• Journal: Science (New York, N.Y.) (Science) Vol. 302 Issue 5645 Pg. 646-50 (Oct 24 2003) ISSN: 1095-9203 [Electronic] United States
• PMID: 14576435 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• GDP dissociation inhibitor 1
• Guanine Nucleotide Dissociation Inhibitors
• Recombinant Proteins
• Saccharomyces cerevisiae Proteins
• Guanosine Diphosphate
• YPT1 protein, S cerevisiae
• rab GTP-Binding Proteins
• Magnesium

Topics

• Binding Sites
• Crystallization
• Crystallography, X-Ray
• Guanine Nucleotide Dissociation Inhibitors (chemistry, genetics, metabolism)
• Guanosine Diphosphate (chemistry, metabolism)
• Hydrogen Bonding
• Hydrophobic and Hydrophilic Interactions
• Lipid Metabolism
• Magnesium (chemistry, metabolism)
• Models, Molecular
• Mutation
• Protein Binding
• Protein Conformation
• Protein Prenylation
• Protein Structure, Secondary
• Protein Structure, Tertiary
• Recombinant Proteins (chemistry, metabolism)
• Saccharomyces cerevisiae Proteins (chemistry, metabolism)
• rab GTP-Binding Proteins (chemistry, metabolism)