6hxu

From Proteopedia

(Difference between revisions)

Revision as of 10:16, 4 December 2019

Crystal structure of Human RHOB Q63L in complex with GTP

Structural highlights

6hxu is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	RHOB, ARH6, ARHB (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6hxu"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6hxu is ON HOLD
+==Crystal structure of Human RHOB Q63L in complex with GTP==
+<StructureSection load='6hxu' size='340' side='right'caption='[[6hxu]], [[Resolution|resolution]] 1.19&Aring;' scene=''>
+== 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>
+</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=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>
+</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.
-Authors: Soulie, S., Gence, R., Cabantous, S., Lajoie-Mazenc, I., Favre, G., Pedelacq, J.D.
+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>
-Description: X-ray structure of a RHOB-GTP
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6hxu" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Cabantous, S]]
-[[Category: Pedelacq, J.D]]
+[[Category: Favre, G]]
 [[Category: Gence, R]]
 [[Category: Lajoie-Mazenc, I]]
+[[Category: Pedelacq, J D]]
 [[Category: Soulie, S]]
-[[Category: Favre, G]]
+[[Category: Antibody]]
+[[Category: Complex]]
+[[Category: Gtpase]]
+[[Category: Immune system]]
+[[Category: Rho]]

6hxu

From Proteopedia

Revision as of 10:16, 4 December 2019

Crystal structure of Human RHOB Q63L in complex with GTP

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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