5tte
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==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=''> | ||
| + | == 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> | ||
| + | </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> | ||
| + | <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='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> | ||
| + | </table> | ||
| + | == 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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:28790309</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5tte" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: E2 ubiquitin-conjugating enzyme]] | ||
| + | [[Category: Lv, Z]] | ||
| + | [[Category: Olsen, S K]] | ||
| + | [[Category: Yuan, L]] | ||
| + | [[Category: Complex]] | ||
| + | [[Category: E2]] | ||
| + | [[Category: Ligase]] | ||
| + | [[Category: Rbr e3 ubiquitin ligase]] | ||
| + | [[Category: Transferase]] | ||
| + | [[Category: Transthioloation]] | ||
Revision as of 07:00, 25 October 2017
Crystal Structure of an RBR E3 ubiquitin ligase in complex with an E2-Ub thioester intermediate mimic
| |||||||||||
