PXD037762

PXD037762 is an original dataset announced via ProteomeXchange.

Title	Erythrocyte invasion-neutralising antibodies prevent Plasmodium falciparum RH5 from binding to basigin-containing membrane protein complexes
Description	Basigin is an essential host receptor for invasion of Plasmodium falciparum into human erythrocytes, interacting with parasite surface protein PfRH5. PfRH5 is a leading blood-stage malaria vaccine candidate and a target of growth-inhibitory antibodies. However, basigin is not alone on the erythrocyte surface. Instead, we show that it is exclusively found in one of two macromolecular complexes, bound predominantly to either plasma membrane Ca2+- ATPase 1/4, PMCA1/4, or monocarboxylate transporter 1, MCT1. PfRH5 binds to either of these complexes with a higher affinity than to isolated basigin ectodomain, making it likely that these are the physiological targets of PfRH5. PMCA-mediated Ca2+ export is not affected by PfRH5, ruling this out as the mechanism underlying changes in calcium flux at the interface between an erythrocyte and the invading parasite. However, our studies rationalise the function of the most effective growth inhibitory antibodies targeting PfRH5. While these antibodies do not reduce the binding of PfRH5 to monomeric basigin, they do reduce its binding to basigin-PMCA and basigin-MCT complexes. This indicates that the most effective PfRH5-targeting antibodies inhibit growth by sterically blocking the essential interaction of PfRH5 with basigin in its physiological context.
HostingRepository	PRIDE
AnnounceDate	2024-07-17
AnnouncementXML	Submission_2024-07-17_05:41:33.101.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD037762
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Alexander Haupt
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	2-pyrrolidone-5-carboxylic acid (Glu); 2-pyrrolidone-5-carboxylic acid (Gln); phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-27 02:44:29	ID requested
⏵ 1	2024-07-17 05:41:33	announced

10.7554/ELIFE.83681;

10.6019/PXD037762;

submitter keyword: AP-MS, membrane protein complex,Erythrocytes, Malaria, Basigin

Prof. Dr. Bernd Fakler
contact affiliation	Institute of Physiology II, University of Freiburg, Germany
contact email	bernd.fakler@physiologie.uni-freiburg.de
lab head
Alexander Haupt
contact affiliation	University of Freiburg, Germany
contact email	alexander.haupt@physiologie.uni-freiburg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD037762
     1. Label: PRIDE project
     2. Name: Erythrocyte invasion-neutralising antibodies prevent Plasmodium falciparum RH5 from binding to basigin-containing membrane protein complexes