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| | ==Structure of HHARI, a RING-IBR-RING ubiquitin ligase: autoinhibition of an Ariadne-family E3 and insights into ligation mechanism== | | ==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]] 3.60Å' scene=''> | + | <StructureSection load='4kc9' size='340' side='right'caption='[[4kc9]], [[Resolution|resolution]] 3.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4kc9]] is a 1 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=4KC9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KC9 FirstGlance]. <br> | + | <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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </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='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4kbl|4kbl]]</td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ARIH1, ARI, MOP6, UBCH7BP, HUSSY-27 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <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=4kc9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kc9 OCA], [http://pdbe.org/4kc9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kc9 RCSB], [http://www.ebi.ac.uk/pdbsum/4kc9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kc9 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Ubiquitin protein ligase|Ubiquitin protein ligase]] | + | *[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Duda, D M]] | + | [[Category: Large Structures]] |
| - | [[Category: Olszewski, J L]] | + | [[Category: Duda DM]] |
| - | [[Category: Schulman, B A]] | + | [[Category: Olszewski JL]] |
| - | [[Category: E3 ubiquitin ligase]] | + | [[Category: Schulman BA]] |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Ring-ibr-ring]]
| + | |
| Structural highlights
Function
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.[1] [2] [3]
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[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tan NG, Ardley HC, Scott GB, Rose SA, Markham AF, Robinson PA. Human homologue of ariadne promotes the ubiquitylation of translation initiation factor 4E homologous protein, 4EHP. FEBS Lett. 2003 Nov 20;554(3):501-4. PMID:14623119
- ↑ Wenzel DM, Lissounov A, Brzovic PS, Klevit RE. UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids. Nature. 2011 Jun 2;474(7349):105-8. doi: 10.1038/nature09966. Epub 2011 May 1. PMID:21532592 doi:10.1038/nature09966
- ↑ Capili AD, Edghill EL, Wu K, Borden KL. Structure of the C-terminal RING finger from a RING-IBR-RING/TRIAD motif reveals a novel zinc-binding domain distinct from a RING. J Mol Biol. 2004 Jul 23;340(5):1117-29. PMID:15236971 doi:10.1016/j.jmb.2004.05.035
- ↑ Duda DM, Olszewski JL, Schuermann JP, Kurinov I, Miller DJ, Nourse A, Alpi AF, Schulman BA. Structure of HHARI, a RING-IBR-RING Ubiquitin Ligase: Autoinhibition of an Ariadne-Family E3 and Insights into Ligation Mechanism. Structure. 2013 Jun 4;21(6):1030-41. doi: 10.1016/j.str.2013.04.019. Epub 2013, May 23. PMID:23707686 doi:10.1016/j.str.2013.04.019
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