The PfPCRCR complex bridges the parasite and erythrocyte membranes. b, Composite model of the PfRCR complex on the erythrocyte membrane, illustrating how the tail of PfRIPR projects towards the merozoite membrane where PfCSS–PfPTRAMP is located. EGF-like domains 5–8 and 9–10 and the CTD of PfRIPR are highlighted. The composite PfRCR complex model is aligned onto the structure of basigin- bound MCT1 (PDB: 7CKR33). For illustrative purposes only, the AlphaFold2- predicted structure of PfPTRAMP (magenta, AlphaFoldDB: Q8I5M8, residues 26–352) and the crystal structure of PfCSS (orange, PDB: 7UNY1) are docked together. c, Mapping of growth-inhibitory antibodies targeting PfRCR components in the context of erythrocyte binding. The potency of growth- inhibitory PfCyRPA-targeting antibodies correlates with their proximity to the erythrocyte membrane, illustrated by overlay of Cy.004 Fab-bound PfCyRPA (PDB: 7PHW5) onto PfRCR–Cy.003. The approximate location of the Fc portion of the intact monoclonal antibody is shown as a faint silhouette through overlay of the crystal structure of an intact antibody (PDB: 1IGT). Growth- inhibitory PfRIPR-targeting antibodies bind to EGF-like domains 5–8, located distal to the erythrocyte membrane.) Farrell B, Alam N, Hart MN, Jamwal A, Ragotte RJ, Walters-Morgan H, Draper SJ, Knuepfer E, Higgins MK. The PfRCR complex bridges malaria parasite and erythrocyte during invasion. Nature. 2024 PMID: 38123677

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