PXD039018

PXD039018 is an original dataset announced via ProteomeXchange.

Title	FKBP35 secures ribosome homeostasis in Plasmodium falciparum
Description	Plasmodium falciparum accounts for the majority of over 600’000 malaria-associated deaths annually. Parasites resistant to nearly all antimalarials have emerged and the need for drugs with alternative modes of action is thus undoubted. The FK506-binding protein PfFKBP35 has gained attention as a promising drug target due to its high affinity to the macrolide compound FK506. Whilst there is considerable interest in targeting PfFKBP35 with small molecules, a genetic validation of this factor as a drug target is missing and its function in parasite biology remains elusive. Here, we show that limiting PfFKBP35 levels are lethal to P. falciparum and result in a delayed-death phenotype that is characterized by defective ribosome homeostasis and protein translation. We furthermore show that the drug exerts it parasiticidal activity in a PfFKBP35-independent manner and, using cellular thermal shift assays, identify FK506-targets beyond PfFKBP35. In addition to revealing first insights on PfFKBP35 function, our results show that current efforts to develop PfFKBP35-targeting drugs need to be reconsidered.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:18:34.206.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Katarzyna Buczak
SpeciesList	scientific name: Plasmodium falciparum; NCBI TaxID: NCBITaxon:5833;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-21 00:56:27	ID requested
1	2023-10-18 08:11:12	announced
⏵ 2	2023-11-14 08:18:34	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: DDA, malaria, LFQ, ribosome homeostasis, Plasmodium falciparum, FK506, FKBP35, antimalarial drugs

Alexander Schmidt
contact affiliation	Proteomics Core Facility, Biozentrum, University of Basel, Switzerland
contact email	alex.schmidt@unibas.ch
lab head
Katarzyna Buczak
contact affiliation	Biozentrum, University of Basel
contact email	katarzyna.buczak@unibas.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD039018
     1. Label: PRIDE project
     2. Name: FKBP35 secures ribosome homeostasis in Plasmodium falciparum