PXD042937-2

PXD042937 is an original dataset announced via ProteomeXchange.

Title	p97/VCP targets Toxoplasma gondii vacuoles for parasite restriction in interferon-stimulated cells
Description	Infection with the parasite Toxoplasma gondii leads to production of interferon gamma (IFN) that stimulates cells to upregulate defence proteins targeting the parasite for cell intrinsic elimination or growth restriction. Various host defence mechanisms operate at the parasitophorous vacuole (PV) in different human cell types leading to PV disruption, acidification, or membrane envelopment. Ubiquitin and p62 are players in all human host control mechanisms of Toxoplasma, but other unifying proteins have not been identified. Here, we show that p97/valosin-containing protein (VCP), as well as its associated proteins ANKRD13A and UBXD1 control Toxoplasma infection while recruited to the PV in IFN-stimulated endothelial cells. Convergent deposition of ANKRD13A, p97/VCP and UBXD1 onto the same vacuole is dependent on vacuolar ubiquitination and observed within 2h post-infection. ANKRD13A, p97/VCP and UBXD1 all drive the acidification mechanism of the vacuole, which is the IFN-dependent control pathway of Toxoplasma in endothelial cells. We assessed p97/VCP in Toxoplasma control in various human cells and demonstrate that p97/VCP is a universal IFN-dependent host restriction factor targeting the Toxoplasma PV in epithelial (HeLa) and endothelial cells (HUVEC), fibroblasts (HFF) and macrophages (THP1).
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:14:29.360.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Barbara Clough
SpeciesList	scientific name: Toxoplasma gondii PRU; NCBI TaxID: 1080348; scientific name: Toxoplasma gondii; NCBI TaxID: NCBITaxon:5811; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-13 02:30:34	ID requested
1	2023-11-15 03:59:54	announced
⏵ 2	2024-10-22 06:14:29	announced	2024-10-22: Updated project metadata.

10.1128/MSPHERE.00511-23;

submitter keyword: innate immunity, UBXD1, ANKRD13A,Toxoplasma gondii, p97/VCP, parasitophorous vacuole, ubiquitin

Eva-Maria Frickel
contact affiliation	Institute for Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham B15 2TT UK
contact email	e.frickel@bham.ac.uk
lab head
Barbara Clough
contact affiliation	Institute for Microbiology and Infection, School of Biosciences, The University of Birmingham, Birmingham B15 2TT
contact email	b.clough@bham.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD042937
     1. Label: PRIDE project
     2. Name: p97/VCP targets Toxoplasma gondii vacuoles for parasite restriction in interferon-stimulated cells