Journal article

Plasmodium falciparum Merozoite Invasion Is Inhibited by Antibodies that Target the PfRh2a and b Binding Domains

Tony Triglia, Lin Chen, Sash Lopaticki, Chaitali Dekiwadia, David T Riglar, Anthony N Hodder, Stuart A Ralph, Jake Baum, Alan F Cowman



Plasmodium falciparum, the causative agent of the most severe form of malaria in humans invades erythrocytes using multiple ligand-receptor interactions. The P. falciparum reticulocyte binding-like homologue proteins (PfRh or PfRBL) are important for entry of the invasive merozoite form of the parasite into red blood cells. We have analysed two members of this protein family, PfRh2a and PfRh2b, and show they undergo a complex series of proteolytic cleavage events before and during merozoite invasion. We show that PfRh2a undergoes a cleavage event in the transmembrane region during invasion consistent with activity of the membrane associated PfROM4 protease that would result in release of the..

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Awarded by Australian Research Council (ARC)

Awarded by NHMRC

Funding Acknowledgements

The infrastructure used was supported by the Victorian State Government OIS and NHMRC IRIISS (#361646) grants; the research was funded by the National Health and Medical Research Council of Australia (NHMRC). D. T. R. was supported through a Pratt Foundation postgraduate scholarship from the University of Melbourne, S. A. R. was supported by Australian Research Council (ARC) Future Fellowships (FT0990350), and J.B. was supported through an NHMRC Career Development Award I (516763) and ARC Future Fellowship (FT100100112). A. F. C. was supported by a Howard Hughes International Scholar and an Australia Fellow from the National Health and Medical Research Council (NHMRC), Australia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.