Guanine Nucleotide Dissociation Inhibitors

Guanine Nucleotide Dissociation Inhibitors. Small GTPases... 

Guanine nucleotide dissociation inhibitors (GDIs) bind to small GTPases and inhibit the dissociation and thus the exchange of the bound nucleotide. 

Kimple, R. J., De Vries, L., Tronchere, H. et al. RGS12 and RGS14 GoLoco motifs are Gai interaction sites with guanine nucleotide dissociation inhibitor activity. J. Biol. Chem. 276 29275-29281,2001. 

Fig. 3 A AGS proteins isolated in yeast-based functional screen G-protein signaling modulator (GPSM) as named by the Human Genome Nomenclature Committee. The major sites of action of AGS proteins in the context of the G-protein activation-deactivation cycle are indicated B on the right. (GPR G-protein regulatory, GEF guanine nucleotide exchange factor, GDI guanine nucleotide dissociation inhibitor, GPCR G-protein coupled receptor)...

AGS3-6—a family of Gai/Gao-specific guanine nucleotide dissociation inhibitors... 

Kimple RJ, DeVries L, Tronchere H, Behe Cl, Morris RA, Gist Farquhar M, Siderovski DP (2001) RGS12 and RGS 14 GoLoco motifs are Galpha(I) interaction sites with guanine nucleotide dissociation inhibitor activity. J Biol Chem 276 29275-29281... 

Dissociation of GDP may be inhibited by specific proteins known as guanine nucleotide dissociation inhibitors (GDI). Proteins with this function are foimd in all members of the Ras family (see Chapter 9). The GDIs have the function, above aU, to provide a cytosohc pool of inactive, GDP-bound proteins (see Chapter 9.1). 

Fig. 1. ADP-ribosylafion of Rho by C3 transferases. Rho proteins are regulated by a GTPase cycle. The GTP-binding proteins ore inactive with GDP bound, and active in the GTP-bound form. GDP/GTP exchange is facilitated by guanine nucleotide dissociation stimulator(s) (GDS) and inhibited by guanine nucleotide dissociation inhibitor(s) (GDI). In the active form, Rho protein interacts with its effector(s) and induces several cellular responses, one of which is polymerization of actin. Rho is ADP-ribosylated by C3 transferases at asparagine-41. Most likely, the modification inhibits the interaction of Rho with its effector(s) which results in inhibition of Rho dependent processes (e.g. F-actin depolymerization)...

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