Divergent roles for the RH5 complex components, CyRPA and RIPR in human-infective malaria parasites

PLoS Pathog. 2019 Jun 11;15(6):e1007809. doi: 10.1371/journal.ppat.1007809. eCollection 2019 Jun.

Abstract

Malaria is caused by Plasmodium parasites, which invade and replicate in erythrocytes. For Plasmodium falciparum, the major cause of severe malaria in humans, a heterotrimeric complex comprised of the secreted parasite proteins, PfCyRPA, PfRIPR and PfRH5 is essential for erythrocyte invasion, mediated by the interaction between PfRH5 and erythrocyte receptor basigin (BSG). However, whilst CyRPA and RIPR are present in most Plasmodium species, RH5 is found only in the small Laverania subgenus. Existence of a complex analogous to PfRH5-PfCyRPA-PfRIPR targeting BSG, and involvement of CyRPA and RIPR in invasion, however, has not been addressed in non-Laverania parasites. Here, we establish that unlike P. falciparum, P. knowlesi and P. vivax do not universally require BSG as a host cell invasion receptor. Although we show that both PkCyRPA and PkRIPR are essential for successful invasion of erythrocytes by P. knowlesi parasites in vitro, neither protein forms a complex with each other or with an RH5-like molecule. Instead, PkRIPR is part of a different trimeric protein complex whereas PkCyRPA appears to function without other parasite binding partners. It therefore appears that in the absence of RH5, outside of the Laverania subgenus, RIPR and CyRPA have different, independent functions crucial for parasite survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basigin / genetics
  • Basigin / metabolism*
  • Humans
  • Malaria / genetics
  • Malaria / metabolism*
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism*
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / metabolism
  • Plasmodium knowlesi / genetics
  • Plasmodium knowlesi / metabolism*
  • Plasmodium vivax / genetics
  • Plasmodium vivax / metabolism
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • Species Specificity

Substances

  • BSG protein, human
  • Multiprotein Complexes
  • Protozoan Proteins
  • Basigin