[HTML][HTML] Structure of the Rho family GTP-binding protein Cdc42 in complex with the multifunctional regulator RhoGDI

GR Hoffman, N Nassar, RA Cerione - Cell, 2000 - cell.com
GR Hoffman, N Nassar, RA Cerione
Cell, 2000cell.com
The RhoGDI proteins serve as key multifunctional regulators of Rho family GTP-binding
proteins. The 2.6 Å 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 …
Abstract
The RhoGDI proteins serve as key multifunctional regulators of Rho family GTP-binding proteins. The 2.6 Å 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 moeity is utilized in this critical regulatory interaction.
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