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| | ==Crystal Structure of an RBR E3 ubiquitin ligase in complex with an E2-Ub thioester intermediate mimic== | | ==Crystal Structure of an RBR E3 ubiquitin ligase in complex with an E2-Ub thioester intermediate mimic== |
| - | <StructureSection load='5tte' size='340' side='right' caption='[[5tte]], [[Resolution|resolution]] 3.50Å' scene=''> | + | <StructureSection load='5tte' size='340' side='right'caption='[[5tte]], [[Resolution|resolution]] 3.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5tte]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TTE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TTE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5tte]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Triticum_aestivum Triticum aestivum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TTE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TTE 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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.501Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/E2_ubiquitin-conjugating_enzyme E2 ubiquitin-conjugating enzyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.23 2.3.2.23] </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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5tte FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tte OCA], [http://pdbe.org/5tte PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tte RCSB], [http://www.ebi.ac.uk/pdbsum/5tte PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tte 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=5tte FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tte OCA], [https://pdbe.org/5tte PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tte RCSB], [https://www.ebi.ac.uk/pdbsum/5tte PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tte 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> [[http://www.uniprot.org/uniprot/UB2L3_HUMAN UB2L3_HUMAN]] Ubiquitin-conjugating enzyme E2 that specifically acts with HECT-type and RBR family E3 ubiquitin-protein ligases. Does not function with most RING-containing E3 ubiquitin-protein ligases because it lacks intrinsic E3-independent reactivity with lysine: in contrast, it has activity with the RBR family E3 enzymes, such as PARK2 and ARIH1, that function like function like RING-HECT hybrids. Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'-linked polyubiquitination. Involved in the selective degradation of short-lived and abnormal proteins. Down-regulated during the S-phase it is involved in progression through the cell cycle. Regulates nuclear hormone receptors transcriptional activity. May play a role in myelopoiesis.<ref>PMID:10888878</ref> <ref>PMID:15367689</ref> <ref>PMID:17003263</ref> <ref>PMID:19340006</ref> <ref>PMID:18946090</ref> <ref>PMID:20061386</ref> <ref>PMID:21532592</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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| | </div> | | </div> |
| | <div class="pdbe-citations 5tte" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5tte" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]] |
| | + | *[[3D structures of ubiquitin|3D structures of ubiquitin]] |
| | + | *[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: E2 ubiquitin-conjugating enzyme]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Lv, Z]] | + | [[Category: Large Structures]] |
| - | [[Category: Olsen, S K]] | + | [[Category: Triticum aestivum]] |
| - | [[Category: Yuan, L]] | + | [[Category: Lv Z]] |
| - | [[Category: Complex]] | + | [[Category: Olsen SK]] |
| - | [[Category: E2]] | + | [[Category: Yuan L]] |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Rbr e3 ubiquitin ligase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Transthioloation]]
| + | |
| 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
RING-in-between-RING (RBR) ubiquitin (Ub) E3 ligases function with Ub E2s through a RING/HECT hybrid mechanism to conjugate Ub to target proteins. Here, we report the crystal structure of the RBR E3, HHARI, in complex with a UbcH7 ~ Ub thioester mimetic which reveals the molecular basis for the specificity of this cognate E2/RBR E3 pair. The structure also reveals mechanistically important conformational changes in the RING1 and UBA-like domains of HHARI that accompany UbcH7 ~ Ub binding and provides a molecular basis by which HHARI recruits E2 ~ Ub in an 'open' conformation. In addition to optimally functioning with an E2 that solely performs transthiolation, our data suggests that HHARI prevents spurious discharge of Ub from E2 to lysine residues by: (1) harboring structural elements that block E2 ~ Ub from adopting a 'closed' conformation and (2) participating in contacts to ubiquitin that promote an open E2 ~ Ub conformation.HHARI is a RING-in-between-RING (RBR) ubiquitin (Ub) E3 ligase. Here the authors present the crystal structure of HHARI with the UbcH7 ~ Ub thioester intermediate mimetic, which reveals that HHARI binds this E2 ~ Ub in an open conformation and explains the specificity of this cognate RBR E3/E2 pair.
Structural insights into the mechanism and E2 specificity of the RBR E3 ubiquitin ligase HHARI.,Yuan L, Lv Z, Atkison JH, Olsen SK Nat Commun. 2017 Aug 8;8(1):211. doi: 10.1038/s41467-017-00272-6. PMID:28790309[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
- ↑ Yuan L, Lv Z, Atkison JH, Olsen SK. Structural insights into the mechanism and E2 specificity of the RBR E3 ubiquitin ligase HHARI. Nat Commun. 2017 Aug 8;8(1):211. doi: 10.1038/s41467-017-00272-6. PMID:28790309 doi:http://dx.doi.org/10.1038/s41467-017-00272-6
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