Structural highlights
Function
[GDIR1_BOVIN] In glioma cells, inhibits cell migration and invasion by mediating the signals of SEMA5A and PLXNB3 that lead to inactivation of RAC1 (By similarity). Regulates the GDP/GTP exchange reaction of the Rho proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP to them.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The Rho GDP-dissociation inhibitors (GDIs) negatively 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 extract 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 of rhoGDI can be attributed to two structurally distinct regions of the protein. A carboxy-terminal folded domain of relative molecular mass 16,000 (M[r] 16K) binds strongly to the Rho-family member Cdc42, yet has little effect on the rate of nucleotide dissociation from the GTPase. The solution structure of this domain shows a beta-sandwich motif with a narrow hydrophobic cleft that binds isoprenes, and an exposed surface that interacts with the protein portion of Cdc42. The amino-terminal region of rhoGDI is unstructured in the absence of target and contributes little to binding, but is necessary to inhibit nucleotide dissociation 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 extraction and inhibition of nucleotide cycling.
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 Jun 19;387(6635):814-9. PMID:9194563[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Fukumoto Y, Kaibuchi K, Hori Y, Fujioka H, Araki S, Ueda T, Kikuchi A, Takai Y. Molecular cloning and characterization of a novel type of regulatory protein (GDI) for the rho proteins, ras p21-like small GTP-binding proteins. Oncogene. 1990 Sep;5(9):1321-8. PMID:2120668
- ↑ Gosser YQ, Nomanbhoy TK, Aghazadeh B, Manor D, Combs C, Cerione RA, Rosen MK. C-terminal binding domain of Rho GDP-dissociation inhibitor directs N-terminal inhibitory peptide to GTPases. Nature. 1997 Jun 19;387(6635):814-9. PMID:9194563 doi:10.1038/42961
- ↑ Gosser YQ, Nomanbhoy TK, Aghazadeh B, Manor D, Combs C, Cerione RA, Rosen MK. C-terminal binding domain of Rho GDP-dissociation inhibitor directs N-terminal inhibitory peptide to GTPases. Nature. 1997 Jun 19;387(6635):814-9. PMID:9194563 doi:10.1038/42961
