at Google ScholarTitle data
Liess, Anna K. L. ; Kucerova, Alena ; Schweimer, Kristian ; Yu, Lu ; Roumeliotis, Theodoros I. ; Diebold, Mathias ; Dybkov, Olexandr ; Sotriffer, Christoph ; Urlaub, Henning ; Choudhary, Jyoti S. ; Mansfeld, Jörg ; Lorenz, Sonja:
Autoinhibition Mechanism of the Ubiquitin-Conjugating Enzyme UBE2S by
Autoubiquitination.
In: Structure.
Vol. 27
(August 2019)
Issue 8
.
- pp. 1195-1210.
ISSN 0969-2126
DOI: https://doi.org/10.1016/j.str.2019.05.008
Abstract in another language
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.
Further data
| Item Type: | Article in a journal |
|---|---|
| Refereed: | Yes |
| Institutions of the University: | Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Former Professors > Chair Biopolymers - Apl. Prof. Dr. Birgitta Wöhrl Faculties Faculties > Faculty of Biology, Chemistry and Earth Sciences Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry with an Emphasis on Biophysical Chemistry Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Former Professors |
| Result of work at the UBT: | Yes |
| DDC Subjects: | 500 Science > 540 Chemistry 500 Science > 570 Life sciences, biology |
| Date Deposited: | 18 Jun 2020 06:36 |
| Last Modified: | 18 Jun 2020 06:36 |
| URI: | https://eref.uni-bayreuth.de/id/eprint/55526 |