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  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., et al. (2019). Autoinhibition mechanism of the ubiquitin-conjugating enzyme UBE2S by autoubiquitination. Structure, 27(8), 1195-1210. doi:10.1016/j.str.2019.05.008.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0003-DDF7-E Version Permalink: http://hdl.handle.net/21.11116/0000-0004-6DB1-A
Genre: Journal Article

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 Creators:
Liess, A. K. L., Author
Kucerova, A., Author
Schweimer, K., Author
Yu, L., Author
Roumeliotis, T. I., Author
Diebold, M., Author
Dybkov, O.1, Author              
Sotriffer, C., Author
Urlaub, H.2, Author              
Choudhary, J. S., Author
Mansfeld, J., Author
Lorenz, S., Author
Affiliations:
1Department of Cellular Biochemistry, MPI for biophysical chemistry, Max Planck Society, ou_578576              
2Research Group of Bioanalytical Mass Spectrometry, MPI for biophysical chemistry, Max Planck Society, ou_578613              

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Free keywords: E2 enzyme; K11 chain; NMR; X-ray crystallography; cell cycle; enzyme mechanism; mass spectrometry; mitosis; molecular dynamics; ubiquitin
 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.

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Language(s): eng - English
 Dates: 2019-06-202019-08-06
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.str.2019.05.008
 Degree: -

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Title: Structure
Source Genre: Journal
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Pages: - Volume / Issue: 27 (8) Sequence Number: - Start / End Page: 1195 - 1210 Identifier: -