title: Structure of the Rho family GTP-binding protein Cdc42 in complex with the multifunctional regulator RhoGDI.
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.
authors.affiliation: Department of Molecular Medicine, Veterinary Medical Center, Cornell University, Ithaca, New York 14853, USA.
authors.forename: G R
authors.initials: GR
authors.lastname: Hoffman
authors.forename: N
authors.initials: N
authors.lastname: Nassar
authors.forename: R A
authors.initials: RA
authors.lastname: Cerione
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004224:Diterpenes / Q000378:metabolism; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000737:chemistry* / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017368:Protein Prenylation; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013499:Surface Properties; D020764:cdc42 GTP-Binding Protein / Q000737:chemistry* / Q000378:metabolism; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
chemical_list: D004224:Diterpenes; D020730:Guanine Nucleotide Dissociation Inhibitors; D008565:Membrane Proteins; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D006153:Guanosine Diphosphate; C017338:geranylgeraniol; D020764:cdc42 GTP-Binding Protein