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5tte

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Revision as of 09:05, 1 January 2020

Crystal Structure of an RBR E3 ubiquitin ligase in complex with an E2-Ub thioester intermediate mimic

Structural highlights

5tte is a 3 chain structure with sequence from Canadian hard winter wheat and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	ARIH1, ARI, MOP6, UBCH7BP, HUSSY-27 (HUMAN), UBE2L3, UBCE7, UBCH7 (HUMAN)
Activity:	E2 ubiquitin-conjugating enzyme, with EC number 2.3.2.23
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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] [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.^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10]

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^[11]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Shimura H, Hattori N, Kubo S, Mizuno Y, Asakawa S, Minoshima S, Shimizu N, Iwai K, Chiba T, Tanaka K, Suzuki T. Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet. 2000 Jul;25(3):302-5. PMID:10888878 doi:10.1038/77060
↑ Verma S, Ismail A, Gao X, Fu G, Li X, O'Malley BW, Nawaz Z. The ubiquitin-conjugating enzyme UBCH7 acts as a coactivator for steroid hormone receptors. Mol Cell Biol. 2004 Oct;24(19):8716-26. PMID:15367689 doi:10.1128/MCB.24.19.8716-8726.2004
↑ Garside H, Waters C, Berry A, Rice L, Ardley HC, White A, Robinson PA, Ray D. UbcH7 interacts with the glucocorticoid receptor and mediates receptor autoregulation. J Endocrinol. 2006 Sep;190(3):621-9. PMID:17003263 doi:10.1677/joe.1.06799
↑ Marteijn JA, van der Meer LT, Smit JJ, Noordermeer SM, Wissink W, Jansen P, Swarts HG, Hibbert RG, de Witte T, Sixma TK, Jansen JH, van der Reijden BA. The ubiquitin ligase Triad1 inhibits myelopoiesis through UbcH7 and Ubc13 interacting domains. Leukemia. 2009 Aug;23(8):1480-9. Epub 2009 Apr 2. PMID:19340006 doi:leu200957
↑ Whitcomb EA, Dudek EJ, Liu Q, Taylor A. Novel control of S phase of the cell cycle by ubiquitin-conjugating enzyme H7. Mol Biol Cell. 2009 Jan;20(1):1-9. doi: 10.1091/mbc.E08-01-0036. Epub 2008 Oct, 22. PMID:18946090 doi:10.1091/mbc.E08-01-0036
↑ David Y, Ziv T, Admon A, Navon A. The E2 ubiquitin conjugating enzymes direct polyubiquitination to preferred lysines. J Biol Chem. 2010 Jan 8. PMID:20061386 doi:M109.089003
↑ 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
↑ 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5tte"

@@ Line 1: / Line 1: @@
 ==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]] 3.50&Aring;' scene=''>
+<StructureSection load='5tte' size='340' side='right'caption='[[5tte]], [[Resolution|resolution]] 3.50&Aring;' 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>
+<table><tr><td colspan='2'>[[5tte]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Canadian_hard_winter_wheat Canadian hard winter wheat] and [http://en.wikipedia.org/wiki/Human Human]. 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='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]), UBE2L3, UBCE7, UBCH7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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>
@@ Line 19: / Line 20: @@
 </div>
 <div class="pdbe-citations 5tte" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Ubiquitin|Ubiquitin]]
+*[[Ubiquitin conjugating enzyme|Ubiquitin conjugating enzyme]]
+*[[Ubiquitin protein ligase|Ubiquitin protein ligase]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Canadian hard winter wheat]]
 [[Category: E2 ubiquitin-conjugating enzyme]]
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Lv, Z]]
 [[Category: Olsen, S K]]

5tte

From Proteopedia

Revision as of 09:05, 1 January 2020

Crystal Structure of an RBR E3 ubiquitin ligase in complex with an E2-Ub thioester intermediate mimic

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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