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dc.contributor.author
Mosadeghi, Ruzbeh
dc.contributor.author
Reichermeier, Kurt M.
dc.contributor.author
Winkler, Martin
dc.contributor.author
Schreiber, Anne
dc.contributor.author
Reitsma, Justin M.
dc.contributor.author
Zhang, Yaru R.
dc.contributor.author
Stengel, Florian
dc.contributor.author
Cao, Junyue
dc.contributor.author
Kim, Minsoo
dc.contributor.author
Sweredoski, Michael J.
dc.contributor.author
Hess, Sonja
dc.contributor.author
Leitner, Alexander
dc.contributor.author
Aebersold, Ruedi
dc.contributor.author
Peter, Matthias
dc.contributor.author
Deshaies, Raymond J.
dc.contributor.author
Enchev, Radoslav I.
dc.date.accessioned
2018-09-11T15:17:54Z
dc.date.available
2017-06-12T07:40:00Z
dc.date.available
2018-09-11T15:17:54Z
dc.date.issued
2016-03
dc.identifier.other
10.7554/eLife.12102
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/117469
dc.identifier.doi
10.3929/ethz-b-000117469
dc.description.abstract
The COP9-Signalosome (CSN) regulates cullin–RING ubiquitin ligase (CRL) activity and assembly by cleaving Nedd8 from cullins. Free CSN is autoinhibited, and it remains unclear how it becomes activated. We combine structural and kinetic analyses to identify mechanisms that contribute to CSN activation and Nedd8 deconjugation. Both CSN and neddylated substrate undergo large conformational changes upon binding, with important roles played by the N-terminal domains of Csn2 and Csn4 and the RING domain of Rbx1 in enabling formation of a high affinity, fully active complex. The RING domain is crucial for deneddylation, and works in part through conformational changes involving insert-2 of Csn6. Nedd8 deconjugation and re-engagement of the active site zinc by the autoinhibitory Csn5 glutamate-104 diminish affinity for Cul1/Rbx1 by ~100-fold, resulting in its rapid ejection from the active site. Together, these mechanisms enable a dynamic deneddylation-disassembly cycle that promotes rapid remodeling of the cellular CRL network.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
eLife Sciences Publications
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Structural and kinetic analysis of the COP9-Signalosome activation and the cullin-RING ubiquitin ligase deneddylation cycle
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
ethz.journal.title
eLife
ethz.journal.volume
5
en_US
ethz.pages.start
e12102
en_US
ethz.size
25 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.identifier.nebis
007613147
ethz.publication.place
Cambridge
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02517 - Institut für Biochemie / Institute of Biochemistry (IBC)::03595 - Peter, Matthias / Peter, Matthias
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02538 - Institut für Molekulare Systembiologie / Institute for Molecular Systems Biology::03663 - Aebersold, Rudolf / Aebersold, Rudolf
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02517 - Institut für Biochemie / Institute of Biochemistry (IBC)::03595 - Peter, Matthias / Peter, Matthias
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02538 - Institut für Molekulare Systembiologie / Institute for Molecular Systems Biology::03663 - Aebersold, Rudolf / Aebersold, Rudolf
ethz.date.deposited
2017-06-12T07:43:28Z
ethz.source
ECIT
ethz.identifier.importid
imp59365479a9be484512
ethz.ecitpid
pub:179376
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-08-01T18:27:31Z
ethz.rosetta.lastUpdated
2018-11-08T02:00:36Z
ethz.rosetta.versionExported
true
ethz.COinS
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