Transferrin receptor 1 is a reticulocyte-specific receptor for <i>Plasmodium vivax</i>.
Lim, Nicholas TY
Schmidt, Christoph Q
Menezes, Maria J
Duraisingh, Manoj T
Science (New York, N.Y.)
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Gruszczyk, J., Kanjee, U., Chan, L., Menant, S., Malleret, B., Lim, N. T., Schmidt, C. Q., et al. (2018). Transferrin receptor 1 is a reticulocyte-specific receptor for <i>Plasmodium vivax</i>.. Science (New York, N.Y.), 359 (6371), 48-55. https://doi.org/10.1126/science.aan1078
Plasmodium vivax shows a strict host tropism for reticulocytes. We identify transferrin receptor 1 (TfR1) as the receptor for P. vivax reticulocyte-binding protein 2b (PvRBP2b). The structure of the N-terminal domain of PvRBP2b involved in red blood cell binding was determined, elucidating the molecular basis for TfR1 recognition. TfR1 was validated as the biological target of PvRBP2b engagement by TfR1 expression knockdown analysis. TfR1 mutant cells deficient in PvRBP2b binding were refractory to invasion of P. vivax, but not to invasion of P. falciparum. Using Brazilian and Thai clinical isolates, we show that PvRBP2b monoclonal antibodies that inhibit reticulocyte binding also block P. vivax entry into reticulocytes. These data show that TfR1-PvRBP2b invasion pathway is critical for the recognition of reticulocytes during P. vivax invasion.
Reticulocytes, Humans, Plasmodium vivax, Malaria, Vivax, Receptors, Transferrin, Membrane Proteins, Protozoan Proteins, Antigens, CD, Crystallography, X-Ray, Host-Parasite Interactions, Gene Knockdown Techniques, Protein Domains
WELLCOME TRUST (108070/Z/15/Z)
Wellcome Trust (090770/Z/09/Z)
External DOI: https://doi.org/10.1126/science.aan1078
This record's URL: https://www.repository.cam.ac.uk/handle/1810/271237