Journal Article

PUBDB-2019-03522

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Autoinhibition Mechanism of the Ubiquitin-Conjugating Enzyme UBE2S by Autoubiquitination

Liess, A. K. L. ; Kucerova, A. ; Schweimer, K. ; Yu, L. ; Roumeliotis, T. I. ; Diebold, M. ; Dybkov, O. ; Sotriffer, C. ; Urlaub, H. ; Choudhary, J. S. ; Mansfeld, J. (Corresponding author) ; Lorenz, S. (Corresponding author)

2019
Cell Press Cambridge, Mass.

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Please use a persistent id in citations: doi:10.1016/j.str.2019.05.008

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.

Note: © Elsevier Ltd.; Post referee fulltext in progress; Embargo 12 months from publication

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Contributing Institute(s):

1. EMBL-User (EMBL-User)

Research Program(s):

1. 6G3 - PETRA III (POF3-622) (POF3-622)

Experiment(s):

1. PETRA Beamline P14 (PETRA III)

Appears in the scientific report 2019

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; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; NCBI Molecular Biology Database ; Nationallizenz ; No Authors Fulltext ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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