PXD033650

PXD033650 is an original dataset announced via ProteomeXchange.

Title	De novo mapping of the apicomplexan Ca2+-responsive proteome: concentration range thermal profiling experiment 2
Description	Apicomplexan parasites cause persistent mortality and morbidity worldwide through diseases including malaria, toxoplasmosis, and cryptosporidiosis. Ca2+ signaling pathways have been repurposed in these eukaryotic pathogens to regulate parasite-specific cellular processes governing the transition between the replicative and lytic phases of the infectious cycle. Despite the presence of conserved Ca2+-responsive proteins, little is known about how specific signaling elements interact to impact pathogenesis. We mapped the Ca2+-responsive proteome of the model apicomplexan T. gondii via time-resolved phosphoproteomics and thermal proteome profiling. The waves of phosphoregulation following PKG activation and stimulated Ca2+ release corroborate known physiological changes but identify specific molecular components in these pathways. Thermal profiling of parasite extracts identified many expected Ca2+-responsive proteins, such as parasite Ca2+-dependent protein kinases. Our approach also identified numerous Ca2+-responsive proteins that are not predicted to bind Ca2+, yet are critical components of the parasite signaling network. We characterized protein phosphatase 1 (PP1) as a Ca2+-responsive enzyme that relocalized to the parasite apex upon Ca2+ store release. Conditional depletion of PP1 revealed that the phosphatase regulates Ca2+ uptake to promote parasite motility. PP1 may thus be partly responsible for Ca2+-regulated serine/threonine phosphatase activity in apicomplexan parasites.
HostingRepository	PRIDE
AnnounceDate	2024-10-07
AnnouncementXML	Submission_2024-10-07_13:46:15.799.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD033650
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Alice Herneisen
SpeciesList	scientific name: Toxoplasma gondii RH; NCBI TaxID: 383379;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; 6x(13)C; methylthiolated residue; 6x(13)C; phosphorylated residue; monohydroxylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-04 15:10:52	ID requested
⏵ 1	2024-10-07 13:46:16	announced

10.7554/elife.80336;

Herneisen AL, Li ZH, Chan AW, Moreno SNJ, Lourido S, -responsive pathways. Elife, 11():(2022) [pubmed]

10.6019/PXD033650;

submitter keyword: Toxoplasma, thermal proteome profiling, proteomics, parasite, calcium signaling, CETSA, TPP, apicomplexan, systems biology

Sebastian Lourido
contact affiliation	Associate Professor, Department of Biology, Massachusetts Institute of Technology and Whitehead Institute of Biomedical Research
contact email	lourido@wi.mit.edu
lab head
Alice Herneisen
contact affiliation	Whitehead Institute for Biomedical Research, Cambridge, MA, USA 02142 Department of Biology, Massachusetts Insitute of Technology
contact email	alice@wi.mit.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD033650
     1. Label: PRIDE project
     2. Name: De novo mapping of the apicomplexan Ca2+-responsive proteome: concentration range thermal profiling experiment 2