| Autor: |
Christopher J. Day, Paola Favuzza, Sabrina Bielfeld, Thomas Haselhorst, Leonie Seefeldt, Julia Hauser, Lucy K. Shewell, Christian Flueck, Jessica Poole, Freda E.-C. Jen, Anja Schäfer, Jean-Pierre Dangy, Tim-W. Gilberger, Camila Tenorio França, Manoj T. Duraisingh, Marco Tamborrini, Nicolas M.B. Brancucci, Christof Grüring, Michael Filarsky, Michael P. Jennings, Gerd Pluschke |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 43, Iss 4, Pp 114012- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2024.114012 |
| Popis: |
Summary: Plasmodium falciparum is a human-adapted apicomplexan parasite that causes the most dangerous form of malaria. P. falciparum cysteine-rich protective antigen (PfCyRPA) is an invasion complex protein essential for erythrocyte invasion. The precise role of PfCyRPA in this process has not been resolved. Here, we show that PfCyRPA is a lectin targeting glycans terminating with α2-6-linked N-acetylneuraminic acid (Neu5Ac). PfCyRPA has a >50-fold binding preference for human, α2-6-linked Neu5Ac over non-human, α2-6-linked N-glycolylneuraminic acid. PfCyRPA lectin sites were predicted by molecular modeling and validated by mutagenesis studies. Transgenic parasite lines expressing endogenous PfCyRPA with single amino acid exchange mutants indicated that the lectin activity of PfCyRPA has an important role in parasite invasion. Blocking PfCyRPA lectin activity with small molecules or with lectin-site-specific monoclonal antibodies can inhibit blood-stage parasite multiplication. Therefore, targeting PfCyRPA lectin activity with drugs, immunotherapy, or a vaccine-primed immune response is a promising strategy to prevent and treat malaria. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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