PXD039646

PXD039646 is an original dataset announced via ProteomeXchange.

Title	Plasmepsin X activates function of the PCRCR complex in P. falciparum by processing PfRh5 for binding to basigin and invasion of human erythrocytes
Description	Plasmodium falciparum causes the most severe form of malaria in humans. The protozoan parasite develops within erythrocytes to mature schizonts, that contain more than 16 merozoites, which egress and invade fresh erythrocytes. The aspartic protease plasmepsin X (PMX), processes proteins and proteases essential for merozoite egress from the schizont and invasion of the host erythrocyte, including the leading vaccine candidate PfRh5. PfRh5 is anchored to the merozoite surface through a 5-membered complex (PCRCR), consisting of Plasmodium thrombospondin-related apical merozoite protein (PTRAMP), cysteine-rich small secreted protein (CSS), Rh5-interacting protein (PfRipr) and cysteine-rich protective antigen (CyRPA). We show that PCRCR is processed by PMX in micronemes to remove the N-terminal prodomain and this activates the function of the complex unmasking a form that can bind basigin on the erythrocyte membrane and mediate merozoite invasion. The ability to activate PCRCR at a specific time in merozoite invasion ensures invasion inhibitory epitopes are exposed to the immune system for a minimal time but also mask potential deleterious effects of its function until they are required. These results provide an important understanding of the essential roles of PMX and the fine regulation of PCRCR function in P. falciparum biology.
HostingRepository	PRIDE
AnnounceDate	2024-10-04
AnnouncementXML	Submission_2024-10-04_02:01:57.551.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Laura Dagley
SpeciesList	scientific name: Plasmodium falciparum (isolate 3D7); NCBI TaxID: 36329;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2023-01-25 03:33:40	ID requested
1	2023-04-04 21:33:41	announced
⏵ 2	2024-10-04 02:01:58	announced	2024-10-04: Updated project metadata.

Triglia T, Scally SW, Seager BA, Pasternak M, Dagley LF, Cowman AF, Plasmepsin X activates the PCRCR complex of Plasmodium falciparum by processing PfRh5 for erythrocyte invasion. Nat Commun, 14(1):2219(2023) [pubmed]

10.1038/s41467-023-37890-2;

submitter keyword: Malaria, plasmepsin X, IP-MS, PCRCR

Professor Alan Cowman
contact affiliation	Deputy Director – Science Strategy The Walter and Eliza Hall institute of Medical Research Professor, Department of Medical Biology Faculty of Medicine, Dentistry and Health The University of Melbourne Australia
contact email	cowman@wehi.edu.au
lab head
Laura Dagley
contact affiliation	WEHI
contact email	dagley.l@wehi.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD039646
     1. Label: PRIDE project
     2. Name: Plasmepsin X activates function of the PCRCR complex in P. falciparum by processing PfRh5 for binding to basigin and invasion of human erythrocytes