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| | <StructureSection load='3dof' size='340' side='right'caption='[[3dof]], [[Resolution|resolution]] 3.30Å' scene=''> | | <StructureSection load='3dof' size='340' side='right'caption='[[3dof]], [[Resolution|resolution]] 3.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3dof]] is a 2 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=3DOF OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=3DOF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3dof]] is a 2 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=3DOF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DOF FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3doe|3doe]]</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://proteopedia.org/fgij/fg.htm?mol=3dof FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dof OCA], [http://pdbe.org/3dof PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3dof RCSB], [http://www.ebi.ac.uk/pdbsum/3dof PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3dof 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=3dof FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dof OCA], [https://pdbe.org/3dof PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dof RCSB], [https://www.ebi.ac.uk/pdbsum/3dof PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dof ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ARL2_HUMAN ARL2_HUMAN]] Small GTP-binding protein which cycles between an inactive GDP-bound and an active GTP-bound form, and the rate of cycling is regulated by guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP). GTP-binding protein that does not act as an allosteric activator of the cholera toxin catalytic subunit. Regulates formation of new microtubules and centrosome integrity. Prevents the TBCD-induced microtubule destruction. Participates in association with TBCD, in the disassembly of the apical junction complexes. Antagonizes the effect of TBCD on epithelial cell detachment and tight and adherens junctions disassembly. Together with ARL2, plays a role in the nuclear translocation, retention and transcriptional activity of STAT3. Component of a regulated secretory pathway involved in Ca(2+)-dependent release of acetylcholine. Required for normal progress through the cell cycle.<ref>PMID:10831612</ref> <ref>PMID:16525022</ref> <ref>PMID:18588884</ref> <ref>PMID:18234692</ref> <ref>PMID:20740604</ref> [[http://www.uniprot.org/uniprot/AR2BP_HUMAN AR2BP_HUMAN]] Together with ARL2, plays a role in the nuclear translocation, retention and transcriptional activity of STAT3. May play a role as an effector of ARL2.<ref>PMID:18234692</ref> | + | [https://www.uniprot.org/uniprot/ARL2_HUMAN ARL2_HUMAN] Small GTP-binding protein which cycles between an inactive GDP-bound and an active GTP-bound form, and the rate of cycling is regulated by guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP). GTP-binding protein that does not act as an allosteric activator of the cholera toxin catalytic subunit. Regulates formation of new microtubules and centrosome integrity. Prevents the TBCD-induced microtubule destruction. Participates in association with TBCD, in the disassembly of the apical junction complexes. Antagonizes the effect of TBCD on epithelial cell detachment and tight and adherens junctions disassembly. Together with ARL2, plays a role in the nuclear translocation, retention and transcriptional activity of STAT3. Component of a regulated secretory pathway involved in Ca(2+)-dependent release of acetylcholine. Required for normal progress through the cell cycle.<ref>PMID:10831612</ref> <ref>PMID:16525022</ref> <ref>PMID:18588884</ref> <ref>PMID:18234692</ref> <ref>PMID:20740604</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ding, J]] | + | [[Category: Ding J]] |
| - | [[Category: Li, S]] | + | [[Category: Li S]] |
| - | [[Category: Zhang, T]] | + | [[Category: Zhang T]] |
| - | [[Category: Adp-ribosylation factor-like 2]]
| + | |
| - | [[Category: Alternative splicing]]
| + | |
| - | [[Category: Binder of arl2]]
| + | |
| - | [[Category: Complex structure]]
| + | |
| - | [[Category: Cytoplasm]]
| + | |
| - | [[Category: Effector]]
| + | |
| - | [[Category: Gtp-binding]]
| + | |
| - | [[Category: Lipoprotein]]
| + | |
| - | [[Category: Mitochondrion]]
| + | |
| - | [[Category: Myristate]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Polymorphism]]
| + | |
| - | [[Category: Signaling protein-hydrolase complex]]
| + | |
| - | [[Category: Small gtpase]]
| + | |
| Structural highlights
Function
ARL2_HUMAN Small GTP-binding protein which cycles between an inactive GDP-bound and an active GTP-bound form, and the rate of cycling is regulated by guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP). GTP-binding protein that does not act as an allosteric activator of the cholera toxin catalytic subunit. Regulates formation of new microtubules and centrosome integrity. Prevents the TBCD-induced microtubule destruction. Participates in association with TBCD, in the disassembly of the apical junction complexes. Antagonizes the effect of TBCD on epithelial cell detachment and tight and adherens junctions disassembly. Together with ARL2, plays a role in the nuclear translocation, retention and transcriptional activity of STAT3. Component of a regulated secretory pathway involved in Ca(2+)-dependent release of acetylcholine. Required for normal progress through the cell cycle.[1] [2] [3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
ARL2 is a member of the ADP-ribosylation factor family but has unique biochemical features. BART is an effector of ARL2 that is essential for nuclear retention of STAT3 and may also be involved in mitochondria transport and apoptosis. Here we report the crystal structure and biochemical characterization of human ARL2-GTP-BART complex. ARL2-GTP assumes a typical small GTPase fold with a unique N-terminal alpha helix conformation. BART consists of a six alpha helix bundle. The interactions between ARL2 and BART involve two interfaces: a conserved N-terminal LLXIL motif of ARL2 is embedded in a hydrophobic cleft of BART and the switch regions of ARL2 interact with helix alpha3 of BART. Both interfaces are essential for the binding as verified by mutagenesis study. This novel recognition and binding mode is different from that of other small GTPase-effector interactions and provides molecular basis for the high specificity of ARL2 for BART.
Crystal structure of the ARL2-GTP-BART complex reveals a novel recognition and binding mode of small GTPase with effector.,Zhang T, Li S, Zhang Y, Zhong C, Lai Z, Ding J Structure. 2009 Apr 15;17(4):602-10. PMID:19368893[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bhamidipati A, Lewis SA, Cowan NJ. ADP ribosylation factor-like protein 2 (Arl2) regulates the interaction of tubulin-folding cofactor D with native tubulin. J Cell Biol. 2000 May 29;149(5):1087-96. PMID:10831612
- ↑ Zhou C, Cunningham L, Marcus AI, Li Y, Kahn RA. Arl2 and Arl3 regulate different microtubule-dependent processes. Mol Biol Cell. 2006 May;17(5):2476-87. Epub 2006 Mar 8. PMID:16525022 doi:http://dx.doi.org/E05-10-0929
- ↑ Veltel S, Kravchenko A, Ismail S, Wittinghofer A. Specificity of Arl2/Arl3 signaling is mediated by a ternary Arl3-effector-GAP complex. FEBS Lett. 2008 Jul 23;582(17):2501-7. Epub 2008 Jun 25. PMID:18588884 doi:http://dx.doi.org/S0014-5793(08)00550-4
- ↑ Muromoto R, Sekine Y, Imoto S, Ikeda O, Okayama T, Sato N, Matsuda T. BART is essential for nuclear retention of STAT3. Int Immunol. 2008 Mar;20(3):395-403. doi: 10.1093/intimm/dxm154. Epub 2008 Jan, 29. PMID:18234692 doi:http://dx.doi.org/10.1093/intimm/dxm154
- ↑ Tian G, Thomas S, Cowan NJ. Effect of TBCD and its regulatory interactor Arl2 on tubulin and microtubule integrity. Cytoskeleton (Hoboken). 2010 Nov;67(11):706-14. doi: 10.1002/cm.20480. PMID:20740604 doi:http://dx.doi.org/10.1002/cm.20480
- ↑ Zhang T, Li S, Zhang Y, Zhong C, Lai Z, Ding J. Crystal structure of the ARL2-GTP-BART complex reveals a novel recognition and binding mode of small GTPase with effector. Structure. 2009 Apr 15;17(4):602-10. PMID:19368893 doi:10.1016/j.str.2009.01.014
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