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| | ==Crystal structure of the human RhoC-GSP complex== | | ==Crystal structure of the human RhoC-GSP complex== |
| - | <StructureSection load='2gcp' size='340' side='right' caption='[[2gcp]], [[Resolution|resolution]] 2.15Å' scene=''> | + | <StructureSection load='2gcp' size='340' side='right'caption='[[2gcp]], [[Resolution|resolution]] 2.15Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2gcp]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GCP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2GCP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2gcp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GCP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GCP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GSP:5-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE'>GSP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.15Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2gcn|2gcn]], [[2gco|2gco]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GSP:5-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE'>GSP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ARH9, ARHC, RHOC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2gcp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gcp OCA], [https://pdbe.org/2gcp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gcp RCSB], [https://www.ebi.ac.uk/pdbsum/2gcp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gcp ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2gcp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gcp OCA], [http://pdbe.org/2gcp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2gcp RCSB], [http://www.ebi.ac.uk/pdbsum/2gcp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2gcp ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RHOC_HUMAN RHOC_HUMAN]] Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Serves as a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Regulates apical junction formation in bronchial epithelial cells.<ref>PMID:16236794</ref> <ref>PMID:20974804</ref> | + | [https://www.uniprot.org/uniprot/RHOC_HUMAN RHOC_HUMAN] Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Serves as a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Regulates apical junction formation in bronchial epithelial cells.<ref>PMID:16236794</ref> <ref>PMID:20974804</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[GTP-binding protein|GTP-binding protein]] | + | *[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]] |
| - | *[[Rho GTPase|Rho GTPase]] | + | *[[Rho GTPase 3D structures|Rho GTPase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Cerione, R A]] | + | [[Category: Large Structures]] |
| - | [[Category: Dias, S M.G]] | + | [[Category: Cerione RA]] |
| - | [[Category: Gtp-binding protein]] | + | [[Category: Dias SMG]] |
| - | [[Category: Gtpase]]
| + | |
| - | [[Category: Signaling protein]]
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| Structural highlights
Function
RHOC_HUMAN Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Serves as a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Regulates apical junction formation in bronchial epithelial cells.[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
RhoC is a member of the Rho family of Ras-related (small) GTPases and shares significant sequence similarity with the founding member of the family, RhoA. However, despite their similarity, RhoA and RhoC exhibit different binding preferences for effector proteins and give rise to distinct cellular outcomes, with RhoC being directly implicated in the invasiveness of cancer cells and the development of metastasis. While the structural analyses of the signaling-active and -inactive states of RhoA have been performed, thus far, the work on RhoC has been limited to an X-ray structure for its complex with the effector protein, mDia1 (for mammalian Diaphanous 1). Therefore, in order to gain insights into the molecular basis for RhoC activation, as well as clues regarding how it mediates distinct cellular responses relative to those induced by RhoA, we have undertaken a structural comparison of RhoC in its GDP-bound (signaling-inactive) state versus its GTP-bound (signaling-active) state as induced by the nonhydrolyzable GTP analogues, guanosine 5'-(beta,gamma-iminotriphosphate) (GppNHp) and guanosine 5'-(3-O-thiotriphosphate) (GTPgammaS). Interestingly, we find that GppNHp-bound RhoC only shows differences in its switch II domain, relative to GDP-bound RhoC, whereas GTPgammaS-bound RhoC exhibits differences in both its switch I and switch II domains. Given that each of the nonhydrolyzable GTP analogues is able to promote the binding of RhoC to effector proteins, these results suggest that RhoC can undergo at least two conformational transitions during its conversion from a signaling-inactive to a signaling-active state, similar to what has recently been proposed for the H-Ras and M-Ras proteins. In contrast, the available X-ray structures for RhoA suggest that it undergoes only a single conformational transition to a signaling-active state. These and other differences regarding the changes in the switch domains accompanying the activation of RhoA and RhoC provide plausible explanations for the functional specificity exhibited by the two GTPases.
X-ray crystal structures reveal two activated states for RhoC.,Dias SM, Cerione RA Biochemistry. 2007 Jun 5;46(22):6547-58. Epub 2007 May 12. PMID:17497936[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kamijo K, Ohara N, Abe M, Uchimura T, Hosoya H, Lee JS, Miki T. Dissecting the role of Rho-mediated signaling in contractile ring formation. Mol Biol Cell. 2006 Jan;17(1):43-55. Epub 2005 Oct 19. PMID:16236794 doi:10.1091/mbc.E05-06-0569
- ↑ Wallace SW, Magalhaes A, Hall A. The Rho target PRK2 regulates apical junction formation in human bronchial epithelial cells. Mol Cell Biol. 2011 Jan;31(1):81-91. doi: 10.1128/MCB.01001-10. Epub 2010 Oct 25. PMID:20974804 doi:10.1128/MCB.01001-10
- ↑ Dias SM, Cerione RA. X-ray crystal structures reveal two activated states for RhoC. Biochemistry. 2007 Jun 5;46(22):6547-58. Epub 2007 May 12. PMID:17497936 doi:10.1021/bi700035p
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