TY  - JOUR
AU  - Day, Christopher J.
AU  - Favuzza, Paola
AU  - Bielfeld, Sabrina
AU  - Haselhorst, Thomas
AU  - Seefeldt, Leonie
AU  - Hauser, Julia
AU  - Shewell, Lucy K.
AU  - Flueck, Christian
AU  - Poole, Jessica
AU  - Jen, Freda E.-C.
AU  - Schäfer, Anja
AU  - Dangy, Jean-Pierre
AU  - Gilberger, Tim-W.
AU  - França, Camila Tenorio
AU  - Duraisingh, Manoj T.
AU  - Tamborrini, Marco
AU  - Brancucci, Nicolas M. B.
AU  - Grüring, Christof
AU  - Filarsky, Michael
AU  - Jennings, Michael P.
AU  - Pluschke, Gerd
TI  - The essential malaria protein PfCyRPA targets glycans to invade erythrocytes
JO  - Cell reports
VL  - 43
IS  - 4
SN  - 2211-1247
CY  - [New York, NY]
PB  - Elsevier
M1  - PUBDB-2024-01367
SP  - 114012
PY  - 2024
AB  - 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. 
LB  - PUB:(DE-HGF)16
C6  - pmid:38573856
UR  - <Go to ISI:>//WOS:001226320900001
DO  - DOI:10.1016/j.celrep.2024.114012
UR  - https://bib-pubdb1.desy.de/record/605249
ER  -