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6jx5

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'''Unreleased structure'''
 
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The entry 6jx5 is ON HOLD
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==Hect domain of AREL1==
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<StructureSection load='6jx5' size='340' side='right'caption='[[6jx5]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[6jx5]] is a 3 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=6JX5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JX5 FirstGlance]. <br>
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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]] 2.402&#8491;</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=6jx5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jx5 OCA], [https://pdbe.org/6jx5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jx5 RCSB], [https://www.ebi.ac.uk/pdbsum/6jx5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jx5 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/AREL1_HUMAN AREL1_HUMAN] E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Inhibits apoptosis by ubiquitinating and targeting for degradation a number of proapoptotic proteins including DIABLO/SMAC, HTRA2 and SEPT4/ARTS which are released from the mitochondrion into the cytosol following apoptotic stimulation.<ref>PMID:23479728</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The HECT E3 ligase family comprises three subfamilies: NEDD4 E3 ubiquitin protein ligase (NEDD4), HECT and RLD domain-containing E3 ubiquitin protein ligase (HERC), and "other." Most previous studies have focused on the NEDD4 subfamily. Apoptosis-resistant E3 ligase 1 (AREL1) belongs to "other" subfamily HECT that inhibits apoptosis by ubiquitinating and degrading proapoptotic proteins. Here, we report the crystal structure of the extended HECT domain of AREL1 (436-823 aa) at 2.4 A resolution and its ubiquitination of the proapoptotic protein second mitochondria-derived activator of caspase (SMAC). We found that the extended HECT domain adopts an inverted, T-shaped, bilobed conformation and harbors an additional loop (567-573 aa) absent in all other HECT members. We also show that the N-terminal extended region (436-482 aa) preceding the HECT domain is indispensable for its stability and activity and that without this region, the HECT domain becomes inactive. AREL1 ubiquitinated SMAC, primarily on Lys-62 and Lys-191. We solved the crystal structure of tetrameric form of SMAC to 2.8 A resolution, revealing the Lys-62 and Lys-191 locations. The AREL1 HECT domain assembled Lys-33-, Lys-48- and Lys-63-linked polyubiquitin chains. Moreover, E701A substitution in the AREL1 HECT domain substantially increased its autopolyubiquitination and SMAC ubiquitination activity, whereas deletion of the last three amino acids at the C terminus completely abrogated AREL1 autoubiquitination and reduced SMAC ubiquitination. Finally, an AREL1-specific ubiquitin variant inhibited SMAC ubiquitination in vitro. Our findings may assist in the development of AREL1 inhibitors that block its anti-apoptotic activity in cancer.
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Authors:
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Structural insights into a HECT-type E3 ligase AREL1 and its ubiquitination activities in vitro.,Singh S, Ng J, Nayak D, Sivaraman J J Biol Chem. 2019 Nov 15. pii: RA119.010327. doi: 10.1074/jbc.RA119.010327. PMID:31732561<ref>PMID:31732561</ref>
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Description:
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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<div class="pdbe-citations 6jx5" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Nayak D]]
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[[Category: Ng J]]
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[[Category: Singh S]]
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[[Category: Sivaraman J]]

Current revision

Hect domain of AREL1

PDB ID 6jx5

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