PXD036746-1

PXD036746 is an original dataset announced via ProteomeXchange.

Title	Function of the Rh5 complex in invasion of human erythrocytes
Description	The most severe form of malaria is caused by Plasmodium falciparum. These parasites invade human erythrocytes and an essential step in this process involves the ligand PfRh5, which forms a complex with CyRPA and PfRipr (RCR complex) and binds basigin on the host cell. We identified a heteromeric disulphide-linked complex consisting of PfPTRAMP and PfCSS and have shown it binds RCR to form a pentameric complex PCRCR. Using P. falciparum lines with conditional knockouts and invasion inhibitory nanobodies to both PfPTRAMP and PfCSS we utilised lattice light-sheet microscopy and show they are essential for merozoite invasion. The PCRCR complex functions to anchor the contact between merozoite and erythrocyte membranes brought together by strong parasite deformations. We solved the structure of nanobody/PfCSS complexes to identify an inhibitory epitope. Our results define the function of the PCRCR complex and identify invasion neutralising epitopes providing a roadmap for structure-guided development of these proteins for a blood stage malaria vaccine.
HostingRepository	PRIDE
AnnounceDate	2022-12-14
AnnouncementXML	Submission_2022-12-14_15:33:51.728.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	LauraDagley
SpeciesList	scientific name: Plasmodium falciparum (isolate 3D7); NCBI TaxID: 36329;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF; timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-14 14:27:08	ID requested
⏵ 1	2022-12-14 15:33:52	announced
2	2023-11-14 08:59:12	announced	2023-11-14: Updated project metadata.

submitter keyword: PfRipr, basigin, PTRAMP, human erythrocytes, invasion complex, PfRh5,malaria, CSS, P. falciparum

AlanCowman
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
LauraDagley
contact affiliation	WEHI
contact email	dagley.l@wehi.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD036746
     1. Label: PRIDE project
     2. Name: Function of the Rh5 complex in invasion of human erythrocytes