PXD006235

PXD006235 is an original dataset announced via ProteomeXchange.

Title	Toxoplasma gondii aspartyl protease 3
Description	The micronemes and rhoptries are specialized organelles that secrete their contents at the apical tip of apicomplexan parasites in a sequential and regulated manner. Microneme and rhoptry proteins crucially participate in motility, invasion, and egress from infected cells. They first traffic through an endosomal-like compartment (ELC) 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 ELC and plays a crucial role 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 (TAILS) between wild type and ASP3 depleted parasites identified microneme and rhoptry proteins as putative ASP3 substrates. The role of ASP3 as maturase for known as well as newly identified organellar proteins is confirmed in vivo and in vitro. A derivative from a series of antimalarial compounds based on a hydroxyethylamine scaffold interrupts the lytic cycle of T. gondii at submicromolar concentration by selectively targeting ASP3.
HostingRepository	PRIDE
AnnounceDate	2018-01-30
AnnouncementXML	Submission_2018-01-30_02:43:18.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tobias Kockmann
SpeciesList	scientific name: Toxoplasma gondii; NCBI TaxID: 5811;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2017-04-03 01:39:04	ID requested
⏵ 1	2018-01-30 02:43:20	announced

Dogga SK, Mukherjee B, Jacot D, Kockmann T, Molino L, Hammoudi PM, Hartkoorn RC, Hehl AB, Soldati-Favre D, A druggable secretory protein maturase of Toxoplasma essential for invasion and egress. Elife, 6():(2017) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: protease substrate screen, TAILS, positional proteomics

Adrian B. Hehl
contact affiliation	Institute of Parasitology, University of Zurich, Zurich, Switzerland
contact email	adrian.hehl@uzh.ch
lab head
Tobias Kockmann
contact affiliation	Functional Genomics Center Zurich
contact email	tobias.kockmann@fgcz.ethz.ch
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/01/PXD006235

PRIDE project URI

• PRIDE
  1. PXD006235
     1. Label: PRIDE project
     2. Name: Toxoplasma gondii aspartyl protease 3