5jcp

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==RhoGAP domain of ARAP3 in complex with RhoA in the transition state==
==RhoGAP domain of ARAP3 in complex with RhoA in the transition state==
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<StructureSection load='5jcp' size='340' side='right' caption='[[5jcp]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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<StructureSection load='5jcp' size='340' side='right'caption='[[5jcp]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5jcp]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JCP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JCP FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5jcp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JCP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JCP FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ALF:TETRAFLUOROALUMINATE+ION'>ALF</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
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<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=5jcp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jcp OCA], [http://pdbe.org/5jcp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jcp RCSB], [http://www.ebi.ac.uk/pdbsum/5jcp PDBsum]</span></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALF:TETRAFLUOROALUMINATE+ION'>ALF</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5jcp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jcp OCA], [https://pdbe.org/5jcp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jcp RCSB], [https://www.ebi.ac.uk/pdbsum/5jcp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jcp ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/ARAP3_HUMAN ARAP3_HUMAN]] Phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members. Is activated by phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) binding. Can be activated by phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding, albeit with lower efficiency. Acts on ARF6, RAC1, RHOA and CDC42. Plays a role in the internalization of anthrax toxin.<ref>PMID:11804589</ref> <ref>PMID:15569923</ref>
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[https://www.uniprot.org/uniprot/RHOA_HUMAN RHOA_HUMAN] Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Involved in a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Plays an essential role in cleavage furrow formation. Required for the apical junction formation of keratinocyte cell-cell adhesion. Serves as a target for the yopT cysteine peptidase from Yersinia pestis, vector of the plague, and Yersinia pseudotuberculosis, which causes gastrointestinal disorders. Stimulates PKN2 kinase activity. May be an activator of PLCE1. Activated by ARHGEF2, which promotes the exchange of GDP for GTP. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity. In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization.<ref>PMID:8910519</ref> <ref>PMID:9121475</ref> <ref>PMID:12900402</ref> <ref>PMID:16103226</ref> <ref>PMID:16236794</ref> <ref>PMID:19934221</ref> <ref>PMID:20937854</ref> <ref>PMID:20974804</ref> [https://www.uniprot.org/uniprot/ARAP3_HUMAN ARAP3_HUMAN] Phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members. Is activated by phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) binding. Can be activated by phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding, albeit with lower efficiency. Acts on ARF6, RAC1, RHOA and CDC42. Plays a role in the internalization of anthrax toxin.<ref>PMID:11804589</ref> <ref>PMID:15569923</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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ARAP3 (Arf-GAP with Rho-GAP domain, ANK repeat, and PH domain-containing protein 3) is unique for its dual specificity GAPs (GTPase-activating protein) activity for Arf6 (ADP-ribosylation factor 6) and RhoA (Ras homolog gene family member A) regulated by phosphatidylinositol 3,4,5-trisphosphate and a small GTPase Rap1-GTP and is involved in regulation of cell shape and adhesion. However, the molecular interface between the ARAP3-RhoGAP domain and RhoA is unknown, as is the substrates specificity of the RhoGAP domain. In this study, we solved the crystal structure of RhoA in complex with the RhoGAP domain of ARAP3. The structure of the complex presented a clear interface between the RhoGAP domain and RhoA. By analyzing the crystal structure and in combination with in vitro GTPase activity assays and isothermal titration calorimetry experiments, we identified the crucial residues affecting RhoGAP activity and substrates specificity among RhoA, Rac1 (Ras-related C3 botulinum toxin substrate 1), and Cdc42 (cell division control protein 42 homolog).
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Structural Basis for the Specific Recognition of RhoA by the Dual GTPase-activating Protein ARAP3.,Bao H, Li F, Wang C, Wang N, Jiang Y, Tang Y, Wu J, Shi Y J Biol Chem. 2016 Aug 5;291(32):16709-19. doi: 10.1074/jbc.M116.736140. Epub 2016, Jun 15. PMID:27311713<ref>PMID:27311713</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 5jcp" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Rho GTPase 3D structures|Rho GTPase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Bao, H]]
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[[Category: Homo sapiens]]
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[[Category: Jiang, Y]]
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[[Category: Large Structures]]
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[[Category: Li, F]]
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[[Category: Synthetic construct]]
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[[Category: Shi, Y]]
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[[Category: Bao H]]
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[[Category: Tang, Y]]
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[[Category: Jiang Y]]
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[[Category: Wang, C]]
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[[Category: Li F]]
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[[Category: Wang, N]]
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[[Category: Shi Y]]
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[[Category: Wu, J]]
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[[Category: Tang Y]]
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[[Category: Arap3]]
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[[Category: Wang C]]
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[[Category: Hydrolase]]
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[[Category: Wang N]]
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[[Category: Rhoa]]
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[[Category: Wu J]]
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[[Category: Rhogap]]
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[[Category: Signaling protein]]
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Current revision

RhoGAP domain of ARAP3 in complex with RhoA in the transition state

PDB ID 5jcp

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