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| | ==Solution Structure of the Catalytic Domain of HHARI== | | ==Solution Structure of the Catalytic Domain of HHARI== |
| - | <StructureSection load='2m9y' size='340' side='right'caption='[[2m9y]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2m9y' size='340' side='right'caption='[[2m9y]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2m9y]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M9Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M9Y FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2m9y]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M9Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M9Y 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='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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ARIH1, ARI, MOP6, UBCH7BP, HUSSY-27 ([https://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'>[https://proteopedia.org/fgij/fg.htm?mol=2m9y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m9y OCA], [https://pdbe.org/2m9y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m9y RCSB], [https://www.ebi.ac.uk/pdbsum/2m9y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m9y 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=2m9y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m9y OCA], [https://pdbe.org/2m9y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m9y RCSB], [https://www.ebi.ac.uk/pdbsum/2m9y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m9y ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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>
| + | [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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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Mercier, P]] | + | [[Category: Mercier P]] |
| - | [[Category: Shaw, G S]] | + | [[Category: Shaw GS]] |
| - | [[Category: Spratt, D E]] | + | [[Category: Spratt DE]] |
| - | [[Category: E3 ligase]]
| + | |
| - | [[Category: Hhari]]
| + | |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Ring2]]
| + | |
| - | [[Category: Zn-binding]]
| + | |
| 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
The ubiquitin-signaling pathway utilizes E1 activating, E2 conjugating, and E3 ligase enzymes to sequentially transfer the small modifier protein ubiquitin to a substrate protein. During the last step of this cascade different types of E3 ligases either act as scaffolds to recruit an E2 enzyme and substrate (RING), or form an ubiquitin-thioester intermediate prior to transferring ubiquitin to a substrate (HECT). The RING-inBetweenRING-RING (RBR) proteins constitute a unique group of E3 ubiquitin ligases that includes the Human Homologue of Drosophila Ariadne (HHARI). These E3 ligases are proposed to use a hybrid RING/HECT mechanism whereby the enzyme uses facets of both the RING and HECT enzymes to transfer ubiquitin to a substrate. We now present the solution structure of the HHARI RING2 domain, the key portion of this E3 ligase required for the RING/HECT hybrid mechanism. The structure shows the domain possesses two Zn(2)(+)-binding sites and a single exposed cysteine used for ubiquitin catalysis. A structural comparison of the RING2 domain with the HECT E3 ligase NEDD4 reveals a near mirror image of the cysteine and histidine residues in the catalytic site. Further, a tandem pair of aromatic residues exists near the C-terminus of the HHARI RING2 domain that is conserved in other RBR E3 ligases. One of these aromatic residues is remotely located from the catalytic site that is reminiscent of the location found in HECT E3 enzymes where it is used for ubiquitin catalysis. These observations provide an initial structural rationale for the RING/HECT hybrid mechanism for ubiquitination used by the RBR E3 ligases.
Structure of the HHARI catalytic domain shows glimpses of a HECT E3 ligase.,Spratt DE, Mercier P, Shaw GS PLoS One. 2013 Aug 15;8(8):e74047. doi: 10.1371/journal.pone.0074047. PMID:24058416[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
- ↑ Spratt DE, Mercier P, Shaw GS. Structure of the HHARI catalytic domain shows glimpses of a HECT E3 ligase. PLoS One. 2013 Aug 15;8(8):e74047. doi: 10.1371/journal.pone.0074047. PMID:24058416 doi:http://dx.doi.org/10.1371/journal.pone.0074047
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