Erythrocyte invasion-neutralising antibodies prevent Plasmodium falciparum RH5 from binding to basigin-containing membrane protein complexes

• DOI: 10.7554/elife.83681
• Publication Date: 2023-10-05T10:15:14Z
• Authors: Abhishek Jamwal; Cristina F Consta...; Stephan Hirschi; Sebastian Henrich; Wolfgang Bildl; Bernd Fakler; Simon J Draper; Uwe Schulte; Matthew K Higgins
• Keywords: Basigin

Basigin is an essential host receptor for invasion of Plasmodium falciparum into human erythrocytes, interacting with parasite surface protein PfRH5. PfRH5 a leading blood-stage malaria vaccine candidate and target growth-inhibitory antibodies. Here, we show that erythrocyte basigin exclusively found in one two macromolecular complexes, bound either to plasma membrane Ca 2+ -ATPase 1/4 (PMCA1/4) or monocarboxylate transporter 1 (MCT1). binds each these complexes higher affinity than isolated ectodomain, making it likely are the physiological targets PMCA-mediated export not affected by PfRH5, unlikely this mechanism underlying changes calcium flux at interface between invading parasite. However, our studies rationalise function most effective antibodies targeting While do reduce binding monomeric basigin, they its basigin-PMCA basigin-MCT complexes. This indicates PfRH5-targeting inhibit growth sterically blocking interaction context.