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==Structure of HHARI, a RING-IBR-RING ubiquitin ligase: autoinhibition of an Ariadne-family E3 and insights into ligation mechanism==
<StructureSection load='4kc9' size='340' side='right'caption='[[4kc9]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4kc9]] is a 1 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=4KC9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KC9 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.603&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <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=4kc9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kc9 OCA], [https://pdbe.org/4kc9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kc9 RCSB], [https://www.ebi.ac.uk/pdbsum/4kc9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kc9 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ARI1_HUMAN ARI1_HUMAN] E3 ubiquitin-protein ligase, which catalyzes polyubiquitination of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3. May play a role in protein translation by mediating polyubiquitination of EIF4E2, leading to its subsequent degradation.<ref>PMID:14623119</ref> <ref>PMID:21532592</ref> <ref>PMID:15236971</ref> 
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== Publication Abstract from PubMed ==
A distinct mechanism for ubiquitin (Ub) ligation has recently been proposed for the RING1-IBR-RING2 (RBR) family of E3s: an N-terminal RING1 domain recruits a thioester-linked intermediate complex between Ub and the E2 UbcH7, and a structurally distinct C-terminal RING2 domain displays a catalytic cysteine required for Ub ligation. To obtain insights into RBR E3s, we determined the crystal structure of the human homolog of Ariadne (HHARI), which reveals the individual RING1, IBR, and RING2 domains embedded in superdomains involving sequences specific to the Ariadne RBR subfamily. The central IBR is flanked on one side by RING1, which is exposed and binds UbcH7. On the other side, a C-terminal autoinhibitory "Ariadne domain" masks the RING2 active site. Insights into RBR E3 mechanisms are provided by structure-based mutations that indicate distinct steps of relief from autoinhibition, Ub transfer from E2 to HHARI, and ligation from the HHARI cysteine to a terminal acceptor.

Structure of HHARI, a RING-IBR-RING Ubiquitin Ligase: Autoinhibition of an Ariadne-Family E3 and Insights into Ligation Mechanism.,Duda DM, Olszewski JL, Schuermann JP, Kurinov I, Miller DJ, Nourse A, Alpi AF, Schulman BA Structure. 2013 Jun 4;21(6):1030-41. doi: 10.1016/j.str.2013.04.019. Epub 2013, May 23. PMID:23707686<ref>PMID:23707686</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4kc9" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Duda DM]]
[[Category: Olszewski JL]]
[[Category: Schulman BA]]