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| <StructureSection load='7od1' size='340' side='right'caption='[[7od1]], [[Resolution|resolution]] 2.45Å' scene=''> | | <StructureSection load='7od1' size='340' side='right'caption='[[7od1]], [[Resolution|resolution]] 2.45Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[7od1]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OD1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OD1 FirstGlance]. <br> | | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OD1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OD1 FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.45Å</td></tr> |
| <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/RBR-type_E3_ubiquitin_transferase RBR-type E3 ubiquitin transferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.31 2.3.2.31] </span></td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7od1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7od1 OCA], [https://pdbe.org/7od1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7od1 RCSB], [https://www.ebi.ac.uk/pdbsum/7od1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7od1 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=7od1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7od1 OCA], [https://pdbe.org/7od1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7od1 RCSB], [https://www.ebi.ac.uk/pdbsum/7od1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7od1 ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function ==
| |
| [[https://www.uniprot.org/uniprot/ARI2_HUMAN ARI2_HUMAN]] E3 ubiquitin-protein ligase, which catalyzes ubiquitination of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3 (PubMed:16118314, PubMed:17646546, PubMed:19340006, PubMed:24076655). Acts as an atypical E3 ubiquitin-protein ligase by working together with cullin-5-RING ubiquitin ligase complex (ECS complex, also named CRL5 complex) and initiating ubiquitination of ECS substrates: associates with ECS complex and specifically mediates addition of the first ubiquitin on ECS targets (By similarity). The initial ubiquitin is then elongated (By similarity). E3 ubiquitin-protein ligase activity is activated upon binding to neddylated form of the ECS complex (PubMed:24076655). Mediates 'Lys-6', 'Lys-48'- and 'Lys-63'-linked polyubiquitination (PubMed:16118314, PubMed:17646546, PubMed:19340006). May play a role in myelopoiesis (PubMed:19340006).[UniProtKB:Q9Y4X5]<ref>PMID:16118314</ref> <ref>PMID:17646546</ref> <ref>PMID:19340006</ref> <ref>PMID:24076655</ref>
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| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| An emerging mechanism of ubiquitylation involves partnering of two distinct E3 ligases. In the best-characterized E3-E3 pathways, ARIH-family RING-between-RING (RBR) E3s ligate ubiquitin to substrates of neddylated cullin-RING E3s. The E3 ARIH2 has been implicated in ubiquitylation of substrates of neddylated CUL5-RBX2-based E3s, including APOBEC3-family substrates of the host E3 hijacked by HIV-1 virion infectivity factor (Vif). However, the structural mechanisms remained elusive. Here structural and biochemical analyses reveal distinctive ARIH2 autoinhibition, and activation on assembly with neddylated CUL5-RBX2. Comparison to structures of E3-E3 assemblies comprising ARIH1 and neddylated CUL1-RBX1-based E3s shows cullin-specific regulation by NEDD8. Whereas CUL1-linked NEDD8 directly recruits ARIH1, CUL5-linked NEDD8 does not bind ARIH2. Instead, the data reveal an allosteric mechanism. NEDD8 uniquely contacts covalently linked CUL5, and elicits structural rearrangements that unveil cryptic ARIH2-binding sites. The data reveal how a ubiquitin-like protein induces protein-protein interactions indirectly, through allostery. Allosteric specificity of ubiquitin-like protein modifications may offer opportunities for therapeutic targeting.
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| CUL5-ARIH2 E3-E3 ubiquitin ligase structure reveals cullin-specific NEDD8 activation.,Kostrhon S, Prabu JR, Baek K, Horn-Ghetko D, von Gronau S, Klugel M, Basquin J, Alpi AF, Schulman BA Nat Chem Biol. 2021 Oct;17(10):1075-1083. doi: 10.1038/s41589-021-00858-8. Epub, 2021 Sep 13. PMID:34518685<ref>PMID:34518685</ref>
| | ==See Also== |
| | | *[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]] |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 7od1" style="background-color:#fffaf0;"></div>
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| == References == | |
| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: RBR-type E3 ubiquitin transferase]]
| | [[Category: Kostrhon SP]] |
| [[Category: Kostrhon, S P]] | | [[Category: Prabu JR]] |
| [[Category: Prabu, J R]] | | [[Category: Schulman BA]] |
| [[Category: Schulman, B A]] | |
| [[Category: Arih2]]
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| [[Category: E3 ligase]]
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| [[Category: Ligase]]
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| [[Category: Rbr]]
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| [[Category: Triad1]]
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| [[Category: Ubiquitin]]
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