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

Prem Prakash, Mohammad Zeeshan, Ekta Saini, Azhar Muneer, Sachin Khurana, Bishwanath Kumar Chourasia, Arunaditya Deshmukh, Inderjeet Kaur, Surabhi Dabral, Niharika Singh, Zille Anam, Ayushi Chaurasiya, Shikha Kaushik, Pradeep Dahiya, Md. Kalamuddin, Jitendra Kumar Thakur, Asif Mohmmed, Anand Ranganathan () and Pawan Malhotra ()
Additional contact information
Prem Prakash: International Centre for Genetic Engineering and Biotechnology (ICGEB)
Mohammad Zeeshan: International Centre for Genetic Engineering and Biotechnology (ICGEB)
Ekta Saini: International Centre for Genetic Engineering and Biotechnology (ICGEB)
Azhar Muneer: International Centre for Genetic Engineering and Biotechnology (ICGEB)
Sachin Khurana: International Centre for Genetic Engineering and Biotechnology (ICGEB)
Bishwanath Kumar Chourasia: International Centre for Genetic Engineering and Biotechnology (ICGEB)
Arunaditya Deshmukh: International Centre for Genetic Engineering and Biotechnology (ICGEB)
Inderjeet Kaur: International Centre for Genetic Engineering and Biotechnology (ICGEB)
Surabhi Dabral: International Centre for Genetic Engineering and Biotechnology (ICGEB)
Niharika Singh: International Centre for Genetic Engineering and Biotechnology (ICGEB)
Zille Anam: Jawaharlal Nehru University
Ayushi Chaurasiya: Jawaharlal Nehru University
Shikha Kaushik: Jawaharlal Nehru University
Pradeep Dahiya: National Institute of Plant Genome Research
Md. Kalamuddin: International Centre for Genetic Engineering and Biotechnology (ICGEB)
Jitendra Kumar Thakur: National Institute of Plant Genome Research
Asif Mohmmed: International Centre for Genetic Engineering and Biotechnology (ICGEB)
Anand Ranganathan: International Centre for Genetic Engineering and Biotechnology (ICGEB)
Pawan Malhotra: International Centre for Genetic Engineering and Biotechnology (ICGEB)

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-01638-6

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