dc.contributor.author | Liess, AKL | |
dc.contributor.author | Kucerova, A | |
dc.contributor.author | Schweimer, K | |
dc.contributor.author | Yu, L | |
dc.contributor.author | Roumeliotis, TI | |
dc.contributor.author | Diebold, M | |
dc.contributor.author | Dybkov, O | |
dc.contributor.author | Sotriffer, C | |
dc.contributor.author | Urlaub, H | |
dc.contributor.author | Choudhary, JS | |
dc.contributor.author | Mansfeld, J | |
dc.contributor.author | Lorenz, S | |
dc.date.accessioned | 2020-09-21T14:31:32Z | |
dc.date.issued | 2019-08-06 | |
dc.identifier.citation | Structure (London, England : 1993), 2019, 27 (8), pp. 1195 - 1210.e7 | |
dc.identifier.issn | 0969-2126 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4075 | |
dc.identifier.eissn | 1878-4186 | |
dc.identifier.doi | 10.1016/j.str.2019.05.008 | |
dc.description.abstract | 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. | |
dc.format | Print-Electronic | |
dc.format.extent | 1195 - 1210.e7 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CELL PRESS | |
dc.rights.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
dc.subject | Cell Line | |
dc.subject | Hela Cells | |
dc.subject | Humans | |
dc.subject | Cysteine | |
dc.subject | Ubiquitin-Conjugating Enzymes | |
dc.subject | Lysine | |
dc.subject | Ubiquitin | |
dc.subject | Crystallography, X-Ray | |
dc.subject | Mitosis | |
dc.subject | Gene Expression Regulation | |
dc.subject | Catalytic Domain | |
dc.subject | Homeostasis | |
dc.subject | Ubiquitination | |
dc.subject | Molecular Dynamics Simulation | |
dc.title | Autoinhibition Mechanism of the Ubiquitin-Conjugating Enzyme UBE2S by Autoubiquitination. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2019-05-17 | |
rioxxterms.versionofrecord | 10.1016/j.str.2019.05.008 | |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2019-08 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Structure (London, England : 1993) | |
pubs.issue | 8 | |
pubs.notes | 12 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-status | Published | |
pubs.volume | 27 | |
pubs.embargo.terms | 12 months | |
icr.researchteam | Post-translational modifications and cell proliferation | |
dc.contributor.icrauthor | Roumeliotis, Theodoros | |
dc.contributor.icrauthor | Choudhary, Jyoti | |
dc.contributor.icrauthor | Mansfeld, Joerg | |