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@ARTICLE{Liess:425979,
author = {Liess, Anna K. L. and Kucerova, Alena and Schweimer,
Kristian and Yu, Lu and Roumeliotis, Theodoros I. and
Diebold, Mathias and Dybkov, Olexandr and Sotriffer,
Christoph and Urlaub, Henning and Choudhary, Jyoti S. and
Mansfeld, Jörg and Lorenz, Sonja},
title = {{A}utoinhibition {M}echanism of the
{U}biquitin-{C}onjugating {E}nzyme {UBE}2{S} by
{A}utoubiquitination},
journal = {Structure},
volume = {27},
number = {8},
issn = {0969-2126},
address = {Cambridge, Mass.},
publisher = {Cell Press},
reportid = {PUBDB-2019-03522},
pages = {1195 - 1210.e7},
year = {2019},
note = {© Elsevier Ltd.; Post referee fulltext in progress;
Embargo 12 months from publication},
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.},
cin = {EMBL-User},
ddc = {540},
cid = {I:(DE-H253)EMBL-User-20120814},
pnm = {6G3 - PETRA III (POF3-622)},
pid = {G:(DE-HGF)POF3-6G3},
experiment = {EXP:(DE-H253)P-P14-20150101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31230944},
UT = {WOS:000478962400005},
doi = {10.1016/j.str.2019.05.008},
url = {https://bib-pubdb1.desy.de/record/425979},
}