Dissociation of Rho GTP:GDP from GDI complex

Stable Identifier
R-HSA-195146
Type
Reaction
Species
Homo sapiens
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GDIs sequester the inactive GTPases, preventing the dissociation of GDP and interactions with regulatory and effector molecules. They maintain Rho GTPases as soluble cytosolic proteins by forming high affinity complexes. In these complexes, the geranylgeranyl membrane targeting moiety present at the C terminus of the Rho GTPases is shielded from the solvent by its insertion into the hydrophobic pocket formed by the immunoglobulin like beta sandwich of the GDI (DerMardirossian and Bokoch, 2005).

Rho proteins, when released from the sequestering cytosolic GDIs, insert into the lipid bilayer of the plasma membrane with their isoprenylated C termini. The membrane bound GEFs activate these free RhoGTPases and thereby trigger the downstream signaling events via respective effector proteins on the membrane (Robbe et al., 2003).

Literature References
PubMed ID Title Journal Year
10655614 The Rac-RhoGDI complex and the structural basis for the regulation of Rho proteins by RhoGDI

Scheffzek, K, Stephan, I, Jensen, ON, Illenberger, D, Gierschik, P

Nat Struct Biol 2000
9194563 C-terminal binding domain of Rho GDP-dissociation inhibitor directs N-terminal inhibitory peptide to GTPases

Gosser, YQ, Nomanbhoy, TK, Aghazadeh, B, Manor, D, Combs, C, Cerione, RA, Rosen, MK

Nature 1997
15921909 GDIs: central regulatory molecules in Rho GTPase activation

DerMardirossian, C, Bokoch, GM

Trends Cell Biol 2005
12471028 Dissociation of GDP dissociation inhibitor and membrane translocation are required for efficient activation of Rac by the Dbl homology-pleckstrin homology region of Tiam

Robbe, K, Otto-Bruc, A, Chardin, P, Antonny, B

J Biol Chem 2003
10676816 Structure of the Rho family GTP-binding protein Cdc42 in complex with the multifunctional regulator RhoGDI

Hoffman, GR, Nassar, N, Cerione, RA

Cell 2000
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