TY  - JOUR
AU  - Liess, Anna K. L.
AU  - Kucerova, Alena
AU  - Schweimer, Kristian
AU  - Yu, Lu
AU  - Roumeliotis, Theodoros I.
AU  - Diebold, Mathias
AU  - Dybkov, Olexandr
AU  - Sotriffer, Christoph
AU  - Urlaub, Henning
AU  - Choudhary, Jyoti S.
AU  - Mansfeld, Jörg
AU  - Lorenz, Sonja
TI  - Autoinhibition Mechanism of the Ubiquitin-Conjugating Enzyme UBE2S by Autoubiquitination
JO  - Structure
VL  - 27
IS  - 8
SN  - 0969-2126
CY  - Cambridge, Mass.
PB  - Cell Press
M1  - PUBDB-2019-03522
SP  - 1195 - 1210.e7
PY  - 2019
N1  - © Elsevier Ltd.; Post referee fulltext in progress; Embargo 12 months from publication
AB  - 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<sup>+5</sup>, to be ubiquitinated intramolecularly. We demonstrate by NMR that the Lys<sup>+5</sup>-linked ubiquitin inhibits UBE2S by obstructing its reloading with ubiquitin. By immunoprecipitation, quantitative mass spectrometry, and siRNA-and-rescue experiments we show that Lys<sup>+5</sup> 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:31230944
UR  - <Go to ISI:>//WOS:000478962400005
DO  - DOI:10.1016/j.str.2019.05.008
UR  - https://bib-pubdb1.desy.de/record/425979
ER  -