PXD015833

PXD015833 is an original dataset announced via ProteomeXchange.

Title	An Exported Kinase Family Mediates Species-Specific Erythrocyte Remodelling and Virulence in Human Malaria
Description	The most severe form of human malaria is caused by Plasmodium falciparum. Its virulence is closely linked to the increase in rigidity and cytoadhesion of infected erythrocytes, which obstruct blood flow to vital organs. Unlike other human-infecting Plasmodium species, P. falciparum exports a family of 18 ‘FIKK’ serine/threonine kinases into the host cell. We reveal substantial species-specific phosphorylation of erythrocyte proteins by P. falciparum, but not by Plasmodium knowlesi, which does not export FIKK kinases. By systematic deletion of all FIKK kinases combined with large-scale quantitative phosphoproteomics we identify unique phosphorylation fingerprints for each kinase, including phosphosites on parasite virulence factors and host cell proteins. Despite their non-overlapping target sites, a network analysis reveals that some FIKKs may act in the same pathways. Only deletion of the non-exported kinase FIKK8 resulted in reduced parasite growth, suggesting the exported FIKKs may support functions important for survival within the host. We show that one kinase, FIKK4.1, mediates both cytoskeletal rigidification and trafficking of the adhesin and key virulence factor PfEMP1 to the host cell surface. This establishes the FIKK family as important drivers of parasite evolution and malaria pathology.
HostingRepository	PRIDE
AnnounceDate	2020-04-17
AnnouncementXML	Submission_2020-04-17_04:02:00.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Malgorzata Broncel
SpeciesList	scientific name: Plasmodium knowlesi strain H; NCBI TaxID: 5851; scientific name: Plasmodium falciparum 3D7; NCBI TaxID: 36329; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-10-15 06:01:17	ID requested
⏵ 1	2020-04-17 04:02:01	announced

Dataset with its publication pending

submitter keyword: Plasmodium, Phosphorylation, Malaria, FIKK kinases, Red blood cell

Moritz Treeck
contact affiliation	Signalling in Apicomplexan Parasites Laboratory, The Francis Crick Institute, London NW1 1AT, UK
contact email	moritz.treeck@crick.ac.uk
lab head
Malgorzata Broncel
contact affiliation	The Francis Crick Institute
contact email	malgorzata.broncel@crick.ac.uk
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/2020/04/PXD015833

PRIDE project URI

• PRIDE
  1. PXD015833
     1. Label: PRIDE project
     2. Name: An Exported Kinase Family Mediates Species-Specific Erythrocyte Remodelling and Virulence in Human Malaria