1AJW
STRUCTURE OF RHOGDI: A C-TERMINAL BINDING DOMAIN TARGETS AN N-TERMINAL INHIBITORY PEPTIDE TO GTPASES, NMR, 20 STRUCTURES
Summary for 1AJW
| Entry DOI | 10.2210/pdb1ajw/pdb |
| Descriptor | RHOGDI (1 entity in total) |
| Functional Keywords | rho-gtpase inhibitor, nucleotide exchange, isoprene binding |
| Biological source | Bos taurus (cattle) |
| Total number of polymer chains | 1 |
| Total formula weight | 16708.01 |
| Authors | Rosen, M.K.,Gosser, Y.Q. (deposition date: 1997-05-11, release date: 1997-11-19, Last modification date: 2024-05-22) |
| Primary citation | Gosser, Y.Q.,Nomanbhoy, T.K.,Aghazadeh, B.,Manor, D.,Combs, C.,Cerione, R.A.,Rosen, M.K. C-terminal binding domain of Rho GDP-dissociation inhibitor directs N-terminal inhibitory peptide to GTPases. Nature, 387:814-819, 1997 Cited by PubMed Abstract: 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. PubMed: 9194563DOI: 10.1038/42961 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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