Human Cyclophilin B forms part of a multi-protein complex during erythrocyte invasion by Plasmodium falciparum

Nat Commun. 2017 Nov 16;8(1):1548. doi: 10.1038/s41467-017-01638-6.

Abstract

Invasion of human erythrocytes by Plasmodium falciparum merozoites involves multiple interactions between host receptors and their merozoite ligands. Here we report human Cyclophilin B as a receptor for PfRhopH3 during merozoite invasion. Localization and binding studies show that Cyclophilin B is present on the erythrocytes and binds strongly to merozoites. We demonstrate that PfRhopH3 binds to the RBCs and their treatment with Cyclosporin A prevents merozoite invasion. We also show a multi-protein complex involving Cyclophilin B and Basigin, as well as PfRhopH3 and PfRh5 that aids the invasion. Furthermore, we report identification of a de novo peptide CDP3 that binds Cyclophilin B and blocks invasion by up to 80%. Collectively, our data provide evidence of compounded interactions between host receptors and merozoite surface proteins and paves the way for developing peptide and small-molecules that inhibit the protein-protein interactions, individually or in toto, leading to abrogation of the invasion process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basigin / metabolism
  • Carrier Proteins / metabolism
  • Cyclophilins / metabolism*
  • Erythrocytes / metabolism*
  • Erythrocytes / parasitology
  • Female
  • Host-Parasite Interactions
  • Humans
  • Merozoites / metabolism
  • Merozoites / physiology
  • Mice, Inbred BALB C
  • Plasmodium falciparum / metabolism*
  • Plasmodium falciparum / physiology
  • Protein Binding
  • Protozoan Proteins / metabolism*
  • Rabbits

Substances

  • Carrier Proteins
  • Protozoan Proteins
  • RH5 protein, Plasmodium falciparum
  • Basigin
  • cyclophilin B
  • Cyclophilins