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

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Title Human Cyclophilin B forms part of a multi-protein complex during erythrocyte invasion by Plasmodium falciparum
 
Creator Prakash, Prem
Zeeshan, Mohammad
Saini, Ekta
Muneer, Azhar
Khurana, Sachin
Chourasia, Bishwanath Kumar
Deshmukh, Arunaditya
Kaur, Inderjeet
Dabral, Surabhi
Singh, Niharika
Anam, Zille
Chaurasiya, Ayushi
Kaushik, Shikha
Dahiya, Pradeep
Kalamuddin, Md.
Thakur, Jitendra K.
Mohmmed, Asif
Ranganathan, Anand
Malhotra, Pawan
 
Subject Malaria
Molecular engineering
Parasite biology
Plasmodium falciparum
erythrocyte invasion
Human Cyclophilin B
 
Description Accepted date: 04 October 2017
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.
We thank Dr Alan F. Cowman and Lin Chen, Infection and Immunity Division, The
Walter and Eliza Hall Institute of Medical Research, Australia for providing PfRh5
protein and antibody and for helpful discussions and a critical reading of this manuscript.
This work was supported by internal grants from the International Centre for
Genetic Engineering and Biotechnology (ICGEB), New Delhi; Department of Biotechnology,
Government of India grant BT/PR7427/BRB/10/1178/2013; and ICMR-CAR
core grant, Special Centre for Molecular Medicine, JNU, New Delhi provided by the
Indian Council for Medical Research, Government of India. P.P., M.Z., A.M. and S.E.
were supported by the Department of Biotechnology, Government of India. The Malaria
Biology group is supported by Programme Support Grant, Indo-Danish Research Grant,
and Grand Challenge Vaccine Program (BT/PR5267/MED/15/87/2012 & BT/IN/Denmark/13/SS/2014)
by the Department of Biotechnology, Government of India. We thank
Dr Sultan Tousif and Prof Gobardhan Das, SCMM, JNU, for help in conducting
experiments related to this study. We thank Rotary blood bank, New Delhi, India, for
providing human red blood cells for Plasmodium cultures. We also thank central
instrumentation facility, NIPGR, New Delhi for SPR experiments. We also thank Manish
Kumar, Advanced Instrumentation Research Facility (AIRF), Jawaharlal Nehru University,
New Delhi for help in Circular Dichroism experiments.
 
Date 2017-11-20T11:53:50Z
2017-11-20T11:53:50Z
2017
 
Type Article
 
Identifier Nature Communications, 8(1): 1548.
2041-1723
http://223.31.159.10:8080/jspui/handle/123456789/800
https://www.nature.com/articles/s41467-017-01638-6
10.1038/s41467-017-01638-6
 
Language en_US
 
Format application/pdf
 
Publisher Nature Publishing Group