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000605249 1001_ $$0P:(DE-HGF)0$$aDay, Christopher J.$$b0
000605249 245__ $$aThe essential malaria protein PfCyRPA targets glycans to invade erythrocytes
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000605249 520__ $$aPlasmodium falciparum is a human-adapted apicomplexan parasite that causes the most dangerous form of malaria. P. falciparum cysteine-rich protective antigen (PfCyRPA) is an invasion complex protein essential for erythrocyte invasion. The precise role of PfCyRPA in this process has not been resolved. Here, we show that PfCyRPA is a lectin targeting glycans terminating with α2-6-linked N-acetylneuraminic acid (Neu5Ac). PfCyRPA has a >50-fold binding preference for human, α2-6-linked Neu5Ac over non-human, α2-6-linked N-glycolylneuraminic acid. PfCyRPA lectin sites were predicted by molecular modeling and validated by mutagenesis studies. Transgenic parasite lines expressing endogenous PfCyRPA with single amino acid exchange mutants indicated that the lectin activity of PfCyRPA has an important role in parasite invasion. Blocking PfCyRPA lectin activity with small molecules or with lectin-site-specific monoclonal antibodies can inhibit blood-stage parasite multiplication. Therefore, targeting PfCyRPA lectin activity with drugs, immunotherapy, or a vaccine-primed immune response is a promising strategy to prevent and treat malaria. 
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000605249 7001_ $$0P:(DE-H253)PIP1087265$$aBielfeld, Sabrina$$b2
000605249 7001_ $$0P:(DE-HGF)0$$aHaselhorst, Thomas$$b3
000605249 7001_ $$0P:(DE-HGF)0$$aSeefeldt, Leonie$$b4
000605249 7001_ $$0P:(DE-HGF)0$$aHauser, Julia$$b5
000605249 7001_ $$0P:(DE-HGF)0$$aShewell, Lucy K.$$b6
000605249 7001_ $$0P:(DE-HGF)0$$aFlueck, Christian$$b7
000605249 7001_ $$0P:(DE-HGF)0$$aPoole, Jessica$$b8
000605249 7001_ $$0P:(DE-HGF)0$$aJen, Freda E.-C.$$b9
000605249 7001_ $$0P:(DE-HGF)0$$aSchäfer, Anja$$b10
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000605249 7001_ $$0P:(DE-HGF)0$$aFrança, Camila Tenorio$$b13
000605249 7001_ $$0P:(DE-HGF)0$$aDuraisingh, Manoj T.$$b14
000605249 7001_ $$0P:(DE-HGF)0$$aTamborrini, Marco$$b15
000605249 7001_ $$0P:(DE-HGF)0$$aBrancucci, Nicolas M. B.$$b16
000605249 7001_ $$0P:(DE-HGF)0$$aGrüring, Christof$$b17
000605249 7001_ $$0P:(DE-H253)PIP1087264$$aFilarsky, Michael$$b18
000605249 7001_ $$0P:(DE-HGF)0$$aJennings, Michael P.$$b19$$eCorresponding author
000605249 7001_ $$00000-0003-1957-2925$$aPluschke, Gerd$$b20$$eCorresponding author
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