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| | ==STRUCTURE OF RHOGDI: A C-TERMINAL BINDING DOMAIN TARGETS AN N-TERMINAL INHIBITORY PEPTIDE TO GTPASES, NMR, MINIMIZED AVERAGE STRUCTURE== | | ==STRUCTURE OF RHOGDI: A C-TERMINAL BINDING DOMAIN TARGETS AN N-TERMINAL INHIBITORY PEPTIDE TO GTPASES, NMR, MINIMIZED AVERAGE STRUCTURE== |
| - | <StructureSection load='1gdf' size='340' side='right'caption='[[1gdf]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''> | + | <StructureSection load='1gdf' size='340' side='right'caption='[[1gdf]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1gdf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bovin Bovin]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GDF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GDF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1gdf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GDF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GDF FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1ajw|1ajw]]</div></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1gdf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gdf OCA], [https://pdbe.org/1gdf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1gdf RCSB], [https://www.ebi.ac.uk/pdbsum/1gdf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1gdf ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1gdf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gdf OCA], [https://pdbe.org/1gdf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1gdf RCSB], [https://www.ebi.ac.uk/pdbsum/1gdf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1gdf ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/GDIR1_BOVIN 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.<ref>PMID:2120668</ref> <ref>PMID:9194563</ref>
| + | [https://www.uniprot.org/uniprot/GDIR1_BOVIN 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.<ref>PMID:2120668</ref> <ref>PMID:9194563</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bovin]] | + | [[Category: Bos taurus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Gosser, Y Q]] | + | [[Category: Gosser YQ]] |
| - | [[Category: Rosen, M K]] | + | [[Category: Rosen MK]] |
| - | [[Category: Isoprene binding]]
| + | |
| - | [[Category: Nucleotide exchange]]
| + | |
| - | [[Category: Rho-gtpase inhibitor]]
| + | |
| 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
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