PCRCR complex is essential for invasion of human erythrocytes by Plasmodium falciparum

• DOI: 10.1038/s41564-022-01261-2
• Publication Date: 2022-11-17T18:13:03Z
• Authors: Stephen W. Scally; Tony Triglia; Cindy Evelyn; Benjamin A. Seager; Michał Pasternak; Pailene S. Lim; Julie Healer; Niall D. Geoghegan; Amy Adair; Wai-Hong Tham; Laura F. Dagley; Kelly L. Rogers; Alan F. Cowman
• Keywords: Basigin

Abstract 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 cysteine-rich protective antigen (CyRPA) PfRh5-interacting protein (PfRipr) (RCR complex) binds basigin on host cell. We identified heteromeric disulfide-linked consisting P. thrombospondin-related apical merozoite (PfPTRAMP) small secreted (PfCSS) have shown that it RCR to pentameric complex, PCRCR. Using lines conditional knockouts, invasion inhibitory nanobodies both PfPTRAMP PfCSS, lattice light-sheet microscopy, we show they are for invasion. PCRCR functions anchor contact between erythrocyte membranes brought together strong parasite deformations. solved structure nanobody–PfCSS complexes identify epitope. Our results define function neutralizing epitopes providing roadmap structure-guided development these proteins blood stage vaccine.