Journal Article

PUBDB-2024-01367

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The essential malaria protein PfCyRPA targets glycans to invade erythrocytes

Day, C. J. ; Favuzza, P. ; Bielfeld, S.Extern*CSSB* ; Haselhorst, T. ; Seefeldt, L. ; Hauser, J. ; Shewell, L. K. ; Flueck, C. ; Poole, J. ; Jen, F. E. -C. ; Schäfer, A. ; Dangy, J.-P. ; Gilberger, T.-W.CSSB* ; França, C. T. ; Duraisingh, M. T. ; Tamborrini, M. ; Brancucci, N. M. B. ; Grüring, C. ; Filarsky, M.Extern*CSSB* ; Jennings, M. P. (Corresponding author) ; Pluschke, G. (Corresponding author)

2024
Elsevier [New York, NY]

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Please use a persistent id in citations: doi:10.1016/j.celrep.2024.114012  doi:10.3204/PUBDB-2024-01367

Abstract: 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.

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Contributing Institute(s):

1. CSSB-BNITM-TG (CSSB-BNITM-TG)
2. CSSB-UHH-MF (CSSB-UHH-MF)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Experiment(s):

1. No specific instrument

Appears in the scientific report 2024

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Database coverage:
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