Journal
NATURE COMMUNICATIONS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-017-01638-6
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Funding
- International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi
- Department of Biotechnology, Government of India [BT/PR7427/BRB/10/1178/2013, BT/PR5267/MED/15/87/2012, BT/IN/Denmark/13/SS/2014]
- ICMR-CAR, Special Centre for Molecular Medicine, JNU, New Delhi by the Indian Council for Medical Research, Government of India
- Department of Biotechnology, Government of India
- Programme Support Grant
- Indo-Danish Research Grant
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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.
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