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

• DOI: 10.1038/s41467-017-01638-6
• Publication Date: 2017-11-10T15:02:10Z
• Authors: Prem Prakash; Mohammad Zeeshan; Ekta Saini; Azhar Muneer; Sachin Khurana; Bishwanath Kumar ...; Arunaditya Deshmukh; Inderjeet Kaur; Surabhi Dabral; Niharika Singh; Zille Anam; Ayushi Chaurasiya; Shikha Kaushik; Pradeep Dahiya; Md. Kalamuddin; Jitendra Kumar Th...; Asif Mohmmed; Anand Ranganathan; Pawan Malhotra
• Keywords: 0301 basic medicine; Mice, Inbred BALB C; Erythrocytes; Merozoites; Science; Q; Plasmodium falciparum; Protozoan Proteins; Article; Host-Parasite Interactions; 3. Good health; Cyclophilins; 03 medical and health sciences; Basigin; Animals; Humans; Female; Rabbits; Carrier Proteins; Protein Binding

AbstractInvasion 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.