View source for 6sge


==Crystal structure of Human RHOB-GTP in complex with nanobody B6==
<StructureSection load='6sge' size='340' side='right'caption='[[6sge]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6sge]] is a 4 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=6SGE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SGE FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5&#8491;</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'>[https://proteopedia.org/fgij/fg.htm?mol=6sge FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sge OCA], [https://pdbe.org/6sge PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6sge RCSB], [https://www.ebi.ac.uk/pdbsum/6sge PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6sge ProSAT]</span></td></tr>
</table>
== Function ==
[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;">
== 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<ref>PMID:31522999</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6sge" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
*[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]]
*[[Rho GTPase 3D structures|Rho GTPase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cabantous S]]
[[Category: Favre G]]
[[Category: Gence R]]
[[Category: Lajoie-Mazenc I]]
[[Category: Pedelacq JD]]
[[Category: Soulie S]]