Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Targeting Plasmodium falciparum Invasion via Antibodies Against Merozoite Surface Enolase That Binds to Band 3 of Human Red Blood Cells

Version 1 : Received: 15 May 2023 / Approved: 16 May 2023 / Online: 16 May 2023 (05:17:02 CEST)

How to cite: Verma, R.; Balaj, C. I.; SAHAL, D.; Sharma, S.; Jarori, G. K. Targeting Plasmodium falciparum Invasion via Antibodies Against Merozoite Surface Enolase That Binds to Band 3 of Human Red Blood Cells. Preprints 2023, 2023051096. https://doi.org/10.20944/preprints202305.1096.v1 Verma, R.; Balaj, C. I.; SAHAL, D.; Sharma, S.; Jarori, G. K. Targeting Plasmodium falciparum Invasion via Antibodies Against Merozoite Surface Enolase That Binds to Band 3 of Human Red Blood Cells. Preprints 2023, 2023051096. https://doi.org/10.20944/preprints202305.1096.v1

Abstract

The antibodies targeting invasive proteins of Plasmodium falciparum (Pf) merozoites is a clever strategy against malaria parasite. The recent finding that Plasmodium merozoites surface enolase is a target for growth neutralizing antibodies has generated interest in identifying its re-ceptor (s) on erythrocytes. In the present study, several biochemical experiments were undertaken involving recombinant Pf enolase and antibody against it to search for its cognate receptor. The binding of rPfeno to erythrocytes was selectively sensitive to trypsin but resistant to neuramini-dase. Failure of yeast enolase binding to human red blood cells under similar conditions indicat-ed high specificity of parasite Pfeno. The mass spectrometric and immunological analyses of pro-teins obtained in pull downs and co-immunoprecipitation samples led to identification of band 3 as an interactor/receptor for Plasmodium enolase. Structural characterization of sequences of band 3 - rPfeno interacting regions revealed C-terminal exocytic regions of band 3 to be binding to Pfeno. Similarly, band 3 binding regions of rPfeno were also identified. Identification of receptor-ligand (band 3: Pfeno) pair paves the way for antimalarial anti-Pf enolase-based vaccine, anti-Pf enolase antibodies as drug and also for developing novel small molecule-based invasion inhibi-tory therapeutics including peptidomimetics that could disrupt the band 3: Pfeno protein-protein interactions.

Keywords

Malaria; Plasmodium enolase; Band 3; antibodies; hRBCghosts

Subject

Biology and Life Sciences, Biology and Biotechnology

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