Resurrection of the ancestral RH5 invasion ligand provides a molecular explanation for the origin of P. falciparum malaria in humans (original) (raw)
Fig 3
RH5 complex interactions are conserved across the Laverania, including the introgressed RH5.
(A) Interactions between the introgressed (Int) and ancestral (Anc) Laverania RH5 complex components are conserved. Introgressed RH5 binds introgressed CyRPA and ancestral P113, and introgressed CyRPA binds ancestral RIPR, as shown by the AVEXIS assay using the named bait and prey proteins. Bars represent means ± SEM; n = 3. (B) Summary of the interactions within the Laverania RH5 complex. The orthologues of RH5, P113, and CyRPA from the named Laverania species were synthesized, expressed, and systematically tested for binding using the AVEXIS assay. The RH5-CyRPA (upper panel) and RH5-P113 (lower panel) interactions were conserved within (indicated by red boxes) and across all tested species, with the exception of P. billcollinsi RH5, which did not interact with P. adleri CyRPA. The scale graphically represents the normalized quantitative readout of the AVEXIS assay but is not expected to provide relative measures of interaction affinity; values above 0.4 are considered positive. Underlying numerical data can be found in S1 Data. A single representative of three experiments is shown. Anc, ancestral; AVEXIS, avidity-based extracellular interaction screening; CyRPA, cysteine-rich protective antigen; HsBSG, human basigin; Int, introgressed; RH5, reticulocyte-binding protein homologue 5; RIPR, RH5-interacting protein; -ve, negative control.