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| | <StructureSection load='6hxu' size='340' side='right'caption='[[6hxu]], [[Resolution|resolution]] 1.19Å' scene=''> | | <StructureSection load='6hxu' size='340' side='right'caption='[[6hxu]], [[Resolution|resolution]] 1.19Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6hxu]] 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=6HXU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HXU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6hxu]] 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=6HXU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HXU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</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]] 1.19Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RHOB, ARH6, ARHB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=6hxu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hxu OCA], [http://pdbe.org/6hxu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hxu RCSB], [http://www.ebi.ac.uk/pdbsum/6hxu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hxu 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=6hxu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hxu OCA], [https://pdbe.org/6hxu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hxu RCSB], [https://www.ebi.ac.uk/pdbsum/6hxu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hxu ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RHOB_HUMAN RHOB_HUMAN]] Mediates apoptosis in neoplastically transformed cells after DNA damage. Not essential for development but affects cell adhesion and growth factor signaling in transformed cells. Plays a negative role in tumorigenesis as deletion causes tumor formation. Involved in intracellular protein trafficking of a number of proteins. Targets PKN1 to endosomes and is involved in trafficking of the EGF receptor from late endosomes to lysosomes. Also required for stability and nuclear trafficking of AKT1/AKT which promotes endothelial cell survival during vascular development. Serves as a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Required for genotoxic stress-induced cell death in breast cancer cells.<ref>PMID:9478917</ref> <ref>PMID:10508588</ref> <ref>PMID:15226397</ref> <ref>PMID:16236794</ref> <ref>PMID:21373644</ref> | + | [https://www.uniprot.org/uniprot/RHOB_HUMAN RHOB_HUMAN] Mediates apoptosis in neoplastically transformed cells after DNA damage. Not essential for development but affects cell adhesion and growth factor signaling in transformed cells. Plays a negative role in tumorigenesis as deletion causes tumor formation. Involved in intracellular protein trafficking of a number of proteins. Targets PKN1 to endosomes and is involved in trafficking of the EGF receptor from late endosomes to lysosomes. Also required for stability and nuclear trafficking of AKT1/AKT which promotes endothelial cell survival during vascular development. Serves as a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Required for genotoxic stress-induced cell death in breast cancer cells.<ref>PMID:9478917</ref> <ref>PMID:10508588</ref> <ref>PMID:15226397</ref> <ref>PMID:16236794</ref> <ref>PMID:21373644</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6hxu" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6hxu" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]] |
| | + | *[[Rho GTPase 3D structures|Rho GTPase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Cabantous, S]] | + | [[Category: Cabantous S]] |
| - | [[Category: Favre, G]] | + | [[Category: Favre G]] |
| - | [[Category: Gence, R]] | + | [[Category: Gence R]] |
| - | [[Category: Lajoie-Mazenc, I]] | + | [[Category: Lajoie-Mazenc I]] |
| - | [[Category: Pedelacq, J D]] | + | [[Category: Pedelacq JD]] |
| - | [[Category: Soulie, S]] | + | [[Category: Soulie S]] |
| - | [[Category: Antibody]]
| + | |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Gtpase]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Rho]]
| + | |
| Structural highlights
Function
RHOB_HUMAN Mediates apoptosis in neoplastically transformed cells after DNA damage. Not essential for development but affects cell adhesion and growth factor signaling in transformed cells. Plays a negative role in tumorigenesis as deletion causes tumor formation. Involved in intracellular protein trafficking of a number of proteins. Targets PKN1 to endosomes and is involved in trafficking of the EGF receptor from late endosomes to lysosomes. Also required for stability and nuclear trafficking of AKT1/AKT which promotes endothelial cell survival during vascular development. Serves as a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Required for genotoxic stress-induced cell death in breast cancer cells.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
The selective downregulation of activated intracellular proteins is a key challenge in cell biology. RHO small GTPases switch between a guanosine diphosphate (GDP)-bound and a guanosine triphosphate (GTP)-bound state that drives downstream signaling. At present, no tool is available to study endogenous RHO-GTPinduced conformational changes in live cells. Here, we established a cell-based screen to selectively degrade RHOB-GTP using F-box-intracellular single-domain antibody fusion. We identified one intracellular antibody (intrabody) that shows selective targeting of endogenous RHOB-GTP mediated by interactions between the CDR3 loop of the domain antibody and the GTP-binding pocket of RHOB. Our results suggest that, while RHOB is highly regulated at the expression level, only the GTP-bound pool, but not its global expression, mediates RHOB functions in genomic instability and in cell invasion. The F-box/intrabody-targeted protein degradation represents a unique approach to knock down the active form of small GTPases or other proteins with multiple cellular activities.
A Targeted Protein Degradation Cell-Based Screening for Nanobodies Selective toward the Cellular RHOB GTP-Bound Conformation.,Bery N, Keller L, Soulie M, Gence R, Iscache AL, Cherier J, Cabantous S, Sordet O, Lajoie-Mazenc I, Pedelacq JD, Favre G, Olichon A Cell Chem Biol. 2019 Nov 21;26(11):1544-1558.e6. doi:, 10.1016/j.chembiol.2019.08.009. Epub 2019 Sep 12. PMID:31522999[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mellor H, Flynn P, Nobes CD, Hall A, Parker PJ. PRK1 is targeted to endosomes by the small GTPase, RhoB. J Biol Chem. 1998 Feb 27;273(9):4811-4. PMID:9478917
- ↑ Gampel A, Parker PJ, Mellor H. Regulation of epidermal growth factor receptor traffic by the small GTPase rhoB. Curr Biol. 1999 Sep 9;9(17):955-8. PMID:10508588
- ↑ Wherlock M, Gampel A, Futter C, Mellor H. Farnesyltransferase inhibitors disrupt EGF receptor traffic through modulation of the RhoB GTPase. J Cell Sci. 2004 Jul 1;117(Pt 15):3221-31. PMID:15226397 doi:http://dx.doi.org/10.1242/jcs.01193
- ↑ 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
- ↑ Srougi MC, Burridge K. The nuclear guanine nucleotide exchange factors Ect2 and Net1 regulate RhoB-mediated cell death after DNA damage. PLoS One. 2011 Feb 23;6(2):e17108. doi: 10.1371/journal.pone.0017108. PMID:21373644 doi:10.1371/journal.pone.0017108
- ↑ Bery N, Keller L, Soulie M, Gence R, Iscache AL, Cherier J, Cabantous S, Sordet O, Lajoie-Mazenc I, Pedelacq JD, Favre G, Olichon A. A Targeted Protein Degradation Cell-Based Screening for Nanobodies Selective toward the Cellular RHOB GTP-Bound Conformation. Cell Chem Biol. 2019 Nov 21;26(11):1544-1558.e6. doi:, 10.1016/j.chembiol.2019.08.009. Epub 2019 Sep 12. PMID:31522999 doi:http://dx.doi.org/10.1016/j.chembiol.2019.08.009
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