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Prakash, Prem; Zeeshan, Mohammad; Saini, Ekta; Muneer, Azhar; Khurana, Sachin; Kumar Chourasia, Bishwanath; Deshmukh, Arunaditya; Kaur, Inderjeet; Dabral, Surabhi; Singh, Niharika; Anam, Zille; Chaurasiya, Ayushi; Kaushik, Shikha; Dahiya, Pradeep; Kalamuddin, Md; Kumar Thakur, Jitendra; Mohmmed, Asif; Ranganathan, Anand; Malhotra, Pawan
Nature communications, 11/2017, Letnik: 8, Številka: 1Journal Article
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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in: SICRIS
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