6sge: Difference between revisions
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The | ==Crystal structure of Human RHOB-GTP in complex with nanobody B6== | ||
<StructureSection load='6sge' size='340' side='right'caption='[[6sge]], [[Resolution|resolution]] 1.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6sge]] is a 4 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=6SGE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6SGE 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> | |||
<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='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=6sge FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sge OCA], [http://pdbe.org/6sge PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6sge RCSB], [http://www.ebi.ac.uk/pdbsum/6sge PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6sge ProSAT]</span></td></tr> | |||
</table> | |||
== 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> | |||
<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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6sge" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Cabantous, S]] | [[Category: Cabantous, S]] | ||
[[Category: | [[Category: Favre, G]] | ||
[[Category: Gence, R]] | [[Category: Gence, R]] | ||
[[Category: Lajoie-Mazenc, I]] | [[Category: Lajoie-Mazenc, I]] | ||
[[Category: Pedelacq, J D]] | |||
[[Category: Soulie, S]] | [[Category: Soulie, S]] | ||
[[Category: | [[Category: Antibody]] | ||
[[Category: Complex]] | |||
[[Category: Gtpase]] | |||
[[Category: Immune system]] | |||
[[Category: Rho]] | |||
