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dc.contributor.author
Sborgi, Lorenzo
dc.contributor.author
Rühl, Sebastian
dc.contributor.author
Mulvihill, Estefania
dc.contributor.author
Pipercevic, Joka
dc.contributor.author
Heilig, Rosalie
dc.contributor.author
Stahlberg, Henning
dc.contributor.author
Farady, Christopher J.
dc.contributor.author
Müller, Daniel J.
dc.contributor.author
Broz, Petr
dc.contributor.author
Hiller, Sebastian
dc.date.accessioned
2021-10-15T08:15:25Z
dc.date.available
2017-06-12T09:40:39Z
dc.date.available
2020-09-10T12:20:38Z
dc.date.available
2021-10-15T08:15:25Z
dc.date.issued
2016-08
dc.identifier.issn
0261-4189
dc.identifier.issn
1460-2075
dc.identifier.other
10.15252/embj.201694696
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/118735
dc.identifier.doi
10.3929/ethz-b-000118735
dc.description.abstract
Pyroptosis is a lytic type of cell death that is initiated by inflammatory caspases. These caspases are activated within multi-protein inflammasome complexes that assemble in response to pathogens and endogenous danger signals. Pyroptotic cell death has been proposed to proceed via the formation of a plasma membrane pore, but the underlying molecular mechanism has remained unclear. Recently, gasdermin D (GSDMD), a member of the ill-characterized gasdermin protein family, was identified as a caspase substrate and an essential mediator of pyroptosis. GSDMD is thus a candidate for pyroptotic pore formation. Here, we characterize GSDMD function in live cells and in vitro. We show that the N-terminal fragment of caspase-1-cleaved GSDMD rapidly targets the membrane fraction of macrophages and that it induces the formation of a plasma membrane pore. In vitro, the N-terminal fragment of caspase-1-cleaved recombinant GSDMD tightly binds liposomes and forms large permeability pores. Visualization of liposome-inserted GSDMD at nanometer resolution by cryo-electron and atomic force microscopy shows circular pores with variable ring diameters around 20 nm. Overall, these data demonstrate that GSDMD is the direct and final executor of pyroptotic cell death.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Wiley
en_US
dc.rights.uri
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject
Atomic force microscopy
en_US
dc.subject
Cell death
en_US
dc.subject
Gasdermin
en_US
dc.subject
Inflammasomes
en_US
dc.subject
Inflammation
en_US
dc.subject
Pyroptosis
en_US
dc.title
GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
dc.date.published
2016-07-14
ethz.journal.title
The EMBO Journal
ethz.journal.volume
35
en_US
ethz.journal.issue
16
en_US
ethz.journal.abbreviated
EMBO J
ethz.pages.start
1766
en_US
ethz.pages.end
1778
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.scopus
ethz.identifier.nebis
010647520
ethz.publication.place
Weinheim
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02060 - Dep. Biosysteme / Dep. of Biosystems Science and Eng.::03870 - Müller, Daniel J. / Müller, Daniel J.
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02060 - Dep. Biosysteme / Dep. of Biosystems Science and Eng.::03870 - Müller, Daniel J. / Müller, Daniel J.
ethz.date.deposited
2017-06-12T09:45:21Z
ethz.source
ECIT
ethz.identifier.importid
imp59365492cdbcb36066
ethz.ecitpid
pub:180701
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-12T11:59:27Z
ethz.rosetta.lastUpdated
2022-03-29T14:15:20Z
ethz.rosetta.versionExported
true
ethz.COinS
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