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
(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.