Resurrection of the ancestral RH5 invasion ligand provides a molecular explanation for the origin of P. falciparum malaria in humans (original) (raw)
Fig 1
RH5 from an ancient inter-clade introgression in Laverania parasites binds both human and gorilla basigin.
(A) Phylogenetic relationships and host tropisms of the parasites within the Laverania subgenus. The inter-clade introgression event encoding rh5 and cyrpa is marked with a yellow arrow. Hosts are indicated as chimpanzee (blue), gorilla (black), and human (red) icons. (B) Organization of the RH5 invasion complex. RH5 is tethered through its N terminus (RH5Nt) to the parasite surface via P113 and binds host basigin on the erythrocyte surface; CyRPA directly interacts with RH5, thereby recruiting RIPR to the complex. (C) Ancestral introgressed RH5 binds to gorilla and human, but not chimpanzee, basigin. Serial dilutions of the indicated concentrations of purified introgressed RH5 were injected over gorilla, human, and chimpanzee basigin immobilized on a sensor chip. Raw surface plasmon resonance (SPR) traces are shown in black and fitted to a simple 1:1 Langmuir binding isotherm (red) to derive the equilibrium dissociation constants (_K_Ds). Underlying numerical data can be found in S1 Data. A representative experiment of three is shown. BSG, basigin; cyrpa, cysteine-rich protective antigen; RH5, reticulocyte-binding protein homologue 5; RH5Ct, RH5 C-terminal domain; RH5Nt, RH5 N-terminal domain; RIPR, RH5-interacting protein; SPR, surface plasmon resonance.