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dc.contributor.author
Dogga, Sunil Kumar
dc.contributor.author
Mukherjee, Budhaditya
dc.contributor.author
Jacot, Damien
dc.contributor.author
Kockmann, Tobias
dc.contributor.author
Molino, Luca
dc.contributor.author
Hammoudi, Pierre-Mehdi
dc.contributor.author
Hartkoorn, Ruben C.
dc.contributor.author
Hehl, Adrian B.
dc.contributor.author
Soldati-Favre, Dominique
dc.date.accessioned
2018-02-16T09:22:12Z
dc.date.available
2017-10-06T02:47:25Z
dc.date.available
2017-11-14T13:46:27Z
dc.date.available
2018-02-16T09:22:12Z
dc.date.available
2018-01-18T14:07:17Z
dc.date.available
2018-02-16T09:21:51Z
dc.date.issued
2017-09-12
dc.identifier.other
10.7554/eLife.27480
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/242297
dc.identifier.doi
10.3929/ethz-b-000191074
dc.description.abstract
Micronemes and rhoptries are specialized secretory organelles that deploy their contents at the apical tip of apicomplexan parasites in a regulated manner. The secretory proteins participate in motility, invasion, and egress and are subjected to proteolytic maturation prior to organellar storage and discharge. Here we establish that Toxoplasma gondii aspartyl protease 3 (ASP3) resides in the endosomal-like compartment and is crucially associated to rhoptry discharge during invasion and to host cell plasma membrane lysis during egress. A comparison of the N-terminome, by terminal amine isotopic labelling of substrates between wild type and ASP3 depleted parasites identified microneme and rhoptry proteins as repertoire of ASP3 substrates. The role of ASP3 as a maturase for previously described and newly identified secretory proteins is confirmed in vivo and in vitro. An antimalarial compound based on a hydroxyethylamine scaffold interrupts the lytic cycle of T. gondii at submicromolar concentration by targeting ASP3.
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
A druggable secretory protein maturase of Toxoplasma essential for invasion and egress
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2017
ethz.journal.title
eLife
ethz.journal.volume
6
en_US
ethz.pages.start
e27480
en_US
ethz.size
35 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Cambridge
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00003 - Schulleitung und Dienste::00022 - Bereich VP Forschung & Wirtschaftsbez. / Domain VP Research & Corporate Relations::02207 - Functional Genomics Center Zürich / Functional Genomics Center Zürich
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00003 - Schulleitung und Dienste::00022 - Bereich VP Forschung & Wirtschaftsbez. / Domain VP Research & Corporate Relations::02207 - Functional Genomics Center Zürich / Functional Genomics Center Zürich
ethz.date.deposited
2017-10-06T02:47:26Z
ethz.source
WOS
ethz.source
BATCH
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2018-02-20T11:11:47Z
ethz.rosetta.lastUpdated
2018-11-06T10:22:56Z
ethz.rosetta.versionExported
true
dc.identifier.olduri
http://hdl.handle.net/20.500.11850/230905
dc.identifier.olduri
http://hdl.handle.net/20.500.11850/191074
ethz.COinS
ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.atitle=A%20druggable%20secretory%20protein%20maturase%20of%20Toxoplasma%20essential%20for%20invasion%20and%20egress&rft.jtitle=eLife&rft.date=2017-09-12&rft.volume=6&rft.spage=e27480&rft.au=Dogga,%20Sunil%20Kumar&Mukherjee,%20Budhaditya&Jacot,%20Damien&Kockmann,%20Tobias&Molino,%20Luca&rft.genre=article&
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