Abstract
The RhoGDI proteins serve as key multifunctional regulators of Rho family GTP-binding proteins. The 2.6 A X-ray crystallographic structure of the Cdc42/RhoGDI complex reveals two important sites of interaction between GDI and Cdc42. First, the amino-terminal regulatory arm of the GDI binds to the switch I and II domains of Cdc42 leading to the inhibition of both GDP dissociation and GTP hydrolysis. Second, the geranylgeranyl moiety of Cdc42 inserts into a hydrophobic pocket within the immunoglobulin-like domain of the GDI molecule leading to membrane release. The structural data demonstrate how GDIs serve as negative regulators of small GTP-binding proteins and how the isoprenoid moiety is utilized in this critical regulatory interaction.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Binding Sites
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Crystallography, X-Ray
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Diterpenes / metabolism
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Guanine Nucleotide Dissociation Inhibitors / chemistry*
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Guanine Nucleotide Dissociation Inhibitors / metabolism
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Guanosine Diphosphate / metabolism
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Membrane Proteins / metabolism
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Models, Molecular
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Molecular Sequence Data
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Protein Binding
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Protein Prenylation
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Sequence Homology, Amino Acid
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Signal Transduction
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Surface Properties
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cdc42 GTP-Binding Protein / chemistry*
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cdc42 GTP-Binding Protein / metabolism
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rho-Specific Guanine Nucleotide Dissociation Inhibitors
Substances
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Diterpenes
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Guanine Nucleotide Dissociation Inhibitors
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Membrane Proteins
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rho-Specific Guanine Nucleotide Dissociation Inhibitors
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Guanosine Diphosphate
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geranylgeraniol
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cdc42 GTP-Binding Protein