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dc.contributor.authorLiess, AKL
dc.contributor.authorKucerova, A
dc.contributor.authorSchweimer, K
dc.contributor.authorYu, L
dc.contributor.authorRoumeliotis, TI
dc.contributor.authorDiebold, M
dc.contributor.authorDybkov, O
dc.contributor.authorSotriffer, C
dc.contributor.authorUrlaub, H
dc.contributor.authorChoudhary, JS
dc.contributor.authorMansfeld, J
dc.contributor.authorLorenz, S
dc.date.accessioned2020-09-21T14:31:32Z
dc.date.issued2019-08-06
dc.identifier.citationStructure (London, England : 1993), 2019, 27 (8), pp. 1195 - 1210.e7
dc.identifier.issn0969-2126
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4075
dc.identifier.eissn1878-4186
dc.identifier.doi10.1016/j.str.2019.05.008
dc.description.abstractUbiquitin-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.
dc.formatPrint-Electronic
dc.format.extent1195 - 1210.e7
dc.languageeng
dc.language.isoeng
dc.publisherCELL PRESS
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved
dc.subjectCell Line
dc.subjectHela Cells
dc.subjectHumans
dc.subjectCysteine
dc.subjectUbiquitin-Conjugating Enzymes
dc.subjectLysine
dc.subjectUbiquitin
dc.subjectCrystallography, X-Ray
dc.subjectMitosis
dc.subjectGene Expression Regulation
dc.subjectCatalytic Domain
dc.subjectHomeostasis
dc.subjectUbiquitination
dc.subjectMolecular Dynamics Simulation
dc.titleAutoinhibition Mechanism of the Ubiquitin-Conjugating Enzyme UBE2S by Autoubiquitination.
dc.typeJournal Article
dcterms.dateAccepted2019-05-17
rioxxterms.versionofrecord10.1016/j.str.2019.05.008
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2019-08
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfStructure (London, England : 1993)
pubs.issue8
pubs.notes12 months
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Post-translational modifications and cell proliferation
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Post-translational modifications and cell proliferation
pubs.publication-statusPublished
pubs.volume27
pubs.embargo.terms12 months
icr.researchteamPost-translational modifications and cell proliferation
dc.contributor.icrauthorRoumeliotis, Theodoros
dc.contributor.icrauthorChoudhary, Jyoti
dc.contributor.icrauthorMansfeld, Joerg


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