Plasmodium falciparum CyRPA glycan binding does not explain adaptation to humans.

Abstract

The human malaria parasite Plasmodium falciparum evolved from a parasite that infects gorillas, termed Plasmodium praefalciparum. The sialic acids on glycans on the surface of erythrocytes differ between humans and other apes. It has recently been shown that the P. falciparum cysteine-rich protective antigen (PfCyRPA) binds human sialoglycans as an essential step in the erythrocyte invasion pathway, while that of the chimpanzee parasite Plasmodium reichenowi has affinities matching ape glycans. Two amino acid changes, at sites 154 and 209, were shown to be sufficient to switch glycan binding preferences and inferred to reflect adaptation of P. falciparum to humans. However, we show that sites 154 and 209 are identical in P. falciparum and P. praefalciparum, with no other differences located in or near the CyRPA glycan binding sites. Thus, the gorilla precursor appears to have already been preadapted to bind human sialoglycans.