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6qhk

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Revision as of 17:31, 14 August 2019

PAO-linked dimer of the catalytic domain of the human ubiquitin-conjugating enzyme UBE2S

Structural highlights

6qhk is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	1zdn
Gene:	UBE2S, E2EPF, OK/SW-cl.73 (HUMAN)
Activity:	E2 ubiquitin-conjugating enzyme, with EC number 2.3.2.23
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[UBE2S_HUMAN] Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. Catalyzes 'Lys-11'-linked polyubiquitination. Acts as an essential factor of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated ubiquitin ligase that controls progression through mitosis. Acts by specifically elongating 'Lys-11'-linked polyubiquitin chains initiated by the E2 enzyme UBE2C/UBCH10 on APC/C substrates, enhancing the degradation of APC/C substrates by the proteasome and promoting mitotic exit. Also acts by elongating ubiquitin chains initiated by the E2 enzyme UBE2D1/UBCH5 in vitro; it is however unclear whether UBE2D1/UBCH5 acts as a E2 enzyme for the APC/C in vivo. Also involved in ubiquitination and subsequent degradation of VHL, resulting in an accumulation of HIF1A. In vitro able to promote polyubiquitination using all 7 ubiquitin Lys residues, except 'Lys-48'-linked polyubiquitination.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

Ubiquitin-conjugating enzymes (E2s) govern key aspects of ubiquitin signaling. Emerging evidence suggests that the activities of E2s are modulated by posttranslational modifications; the structural underpinnings, however, are largely unclear. Here, we unravel the structural basis and mechanistic consequences of a conserved autoubiquitination event near the catalytic center of E2s, using the human anaphase-promoting complex/cyclosome-associated UBE2S as a model system. Crystal structures we determined of the catalytic ubiquitin carrier protein domain combined with MD simulations reveal that the active-site region is malleable, which permits an adjacent ubiquitin acceptor site, Lys(+5), to be ubiquitinated intramolecularly. We demonstrate by NMR that the Lys(+5)-linked ubiquitin inhibits UBE2S by obstructing its reloading with ubiquitin. By immunoprecipitation, quantitative mass spectrometry, and siRNA-and-rescue experiments we show that Lys(+5) ubiquitination of UBE2S decreases during mitotic exit but does not influence proteasomal turnover of this E2. These findings suggest that UBE2S activity underlies inherent regulation during the cell cycle.

Autoinhibition Mechanism of the Ubiquitin-Conjugating Enzyme UBE2S by Autoubiquitination.,Liess AKL, Kucerova A, Schweimer K, Yu L, Roumeliotis TI, Diebold M, Dybkov O, Sotriffer C, Urlaub H, Choudhary JS, Mansfeld J, Lorenz S Structure. 2019 Jun 4. pii: S0969-2126(19)30170-4. doi:, 10.1016/j.str.2019.05.008. PMID:31230944^[6]

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

References

↑ Jung CR, Hwang KS, Yoo J, Cho WK, Kim JM, Kim WH, Im DS. E2-EPF UCP targets pVHL for degradation and associates with tumor growth and metastasis. Nat Med. 2006 Jul;12(7):809-16. Epub 2006 Jul 2. PMID:16819549 doi:http://dx.doi.org/10.1038/nm1440
↑ Garnett MJ, Mansfeld J, Godwin C, Matsusaka T, Wu J, Russell P, Pines J, Venkitaraman AR. UBE2S elongates ubiquitin chains on APC/C substrates to promote mitotic exit. Nat Cell Biol. 2009 Nov;11(11):1363-9. doi: 10.1038/ncb1983. Epub 2009 Oct 11. PMID:19820702 doi:http://dx.doi.org/10.1038/ncb1983
↑ Williamson A, Wickliffe KE, Mellone BG, Song L, Karpen GH, Rape M. Identification of a physiological E2 module for the human anaphase-promoting complex. Proc Natl Acad Sci U S A. 2009 Oct 27;106(43):18213-8. doi:, 10.1073/pnas.0907887106. Epub 2009 Oct 12. PMID:19822757 doi:http://dx.doi.org/10.1073/pnas.0907887106
↑ 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
↑ Bremm A, Freund SM, Komander D. Lys11-linked ubiquitin chains adopt compact conformations and are preferentially hydrolyzed by the deubiquitinase Cezanne. Nat Struct Mol Biol. 2010 Aug;17(8):939-47. Epub 2010 Jul 11. PMID:20622874 doi:10.1038/nsmb.1873
↑ Liess AKL, Kucerova A, Schweimer K, Yu L, Roumeliotis TI, Diebold M, Dybkov O, Sotriffer C, Urlaub H, Choudhary JS, Mansfeld J, Lorenz S. Autoinhibition Mechanism of the Ubiquitin-Conjugating Enzyme UBE2S by Autoubiquitination. Structure. 2019 Jun 4. pii: S0969-2126(19)30170-4. doi:, 10.1016/j.str.2019.05.008. PMID:31230944 doi:http://dx.doi.org/10.1016/j.str.2019.05.008

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6qhk"

@@ Line 3: / Line 3: @@
 <StructureSection load='6qhk' size='340' side='right'caption='[[6qhk]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6qhk]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QHK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QHK FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6qhk]] is a 2 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=6QHK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QHK FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PA0:PHENYLARSINE+OXIDE'>PA0</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1zdn|1zdn]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UBE2S, E2EPF, OK/SW-cl.73 ([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=6qhk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qhk OCA], [http://pdbe.org/6qhk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qhk RCSB], [http://www.ebi.ac.uk/pdbsum/6qhk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qhk ProSAT]</span></td></tr>
@@ Line 25: / Line 26: @@
 </StructureSection>
 [[Category: E2 ubiquitin-conjugating enzyme]]
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Liess, A K.L]]

6qhk

From Proteopedia

Revision as of 17:31, 14 August 2019

PAO-linked dimer of the catalytic domain of the human ubiquitin-conjugating enzyme UBE2S

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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