Detail of "133312-85-3"

Reference

C-terminal binding domain of Rho GDP-dissociation inhibitor directs N-terminal inhibitory peptide to GTPases

C-terminal binding domain of Rho GDP-dissociation inhibitor directs N-terminal inhibitory peptide to GTPases. Gosser, Yuying Q.; Nomanbhoy, Tyzoon K.; Aghazadeh, Behzad; Manor, Danny; Combs, Carolyn; Cerione, Richard A.; Rosen, Michael K. (Cellular Biochem. and Biphyscis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA). Nature (London), 387(6635), 814-819 (English) 1997 Macmillan Magazines. CODEN: NATUAS. ISSN: 0028-0836. DOCUMENT TYPE: Journal CA Section: 7 (Enzymes) Section cross-reference(s): 6 The Rho GDP-dissocn. inhibitors (GDIs) neg. regulate Rho-family GTPases. The inhibitory activity of GDI derives both from an ability to bind the carboxy-terminal isoprene of Rho family members and ext. them from membranes, and from inhibition of GTPase cycling between the GTP- and GDP-bound states. Here we demonstrate that these binding and inhibitory functions or rhoGDI can be attributed to two structurally distinct regions of the protein. A carboxy-terminal folded domain of relative mol. mass 16,000 (Mr 16K) binds strongly to the Rho-family member Cdc42, yet has little effect on the rate of nucleotide dissocn. from the GTPase. The soln. structure of this domain shows a b-sandwich motif with a narrow hydrophobic cleft that binds isoprenes, and an exposed surface that interacts with the protein portion of Cdc42. 133312-85-3 which is the cas registry number is also used here. The amino-terminal region of rhoGDI is unstructured in the absence of target and contributes little to binding, but is necessary to inhibit nucleotide dissocn. from Cdc42. These results lead to a model of rhoGDI function in which the carboxy-terminal binding domain targets the amino-terminal inhibitory region to GTPases, resulting in membrane extn. and inhibition of nucleotide cycling. .