Lee, Seong-Kyun, Crosnier, Cécile orcid.org/0000-0003-0619-9797, Valenzuela-Leon, Paola Carolina et al. (7 more authors) (2024) Complement receptor 1 is the human erythrocyte receptor for Plasmodium vivax erythrocyte binding protein. Proceedings of the National Academy of Sciences of the United States of America. e2316304121. ISSN 1091-6490
Abstract
The discovery that Africans were resistant to infection by Plasmodium vivax ( P. vivax) led to the conclusion that P. vivax invasion relied on the P. vivax Duffy Binding Protein (PvDBP) interacting with the Duffy Antigen Receptor for Chemokines (DARC) expressed on erythrocytes. However, the recent reporting of P. vivax infections in DARC-negative Africans suggests that the parasite might use an alternate invasion pathway to infect DARC-negative reticulocytes. To identify the parasite ligands and erythrocyte receptors that enable P. vivax invasion of both DARC-positive and -negative erythrocytes, we expressed region II containing the Duffy Binding-Like (DBL) domain of P. vivax erythrocyte binding protein (PvEBP-RII) and verified that the DBL domain binds to both DARC-positive and -negative erythrocytes. Furthermore, an AVidity-based EXtracelluar Interaction Screening (AVEXIS) was used to identify the receptor for PvEBP among over 750 human cell surface receptor proteins, and this approach identified only Complement Receptor 1 (CR1, CD35, or C3b/C4b receptor) as a PvEBP receptor. CR1 is a well-known receptor for P. falciparum Reticulocyte binding protein Homology 4 (PfRh4) and is present on the surfaces of both reticulocytes and normocytes, but its expression decreases as erythrocytes age. Indeed, PvEBP-RII bound to a subpopulation of both reticulocytes and normocytes, and this binding was blocked by the addition of soluble CR1 recombinant protein, indicating that CR1 is the receptor of PvEBP. In addition, we found that the Long Homology Repeat A (LHR-A) subdomain of CR1 is the only subdomain responsible for mediating the interaction with PvEBP-RII.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 the Author(s). Published by PNAS. |
Keywords: | Humans,Plasmodium vivax,Receptors, Cell Surface,Erythrocytes,Reticulocytes,CD2 Antigens,Cell Adhesion Molecules,Malaria, Falciparum |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Hull York Medical School (York) The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 19 Feb 2024 12:00 |
Last Modified: | 05 Mar 2025 00:09 |
Published Version: | https://doi.org/10.1073/pnas.2316304121 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1073/pnas.2316304121 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:209360 |
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Description: lee-et-al-2024-complement-receptor-1-is-the-human-erythrocyte-receptor-for-plasmodium-vivax-erythrocyte-binding-protein
Licence: CC-BY-NC-ND 2.5