Plasmodium falciparum Adhesion Domains Linked to Severe Malaria Differ in Blockade of Endothelial Protein C Receptor

Sampath S, et al., DOI: 10.1111/cmi.12478, Cell Microbiol, 2015

Domain cassette 8 (DC8) and DC13 of Plasmodium falciparum are responsible for severe malaria and demonstrate different endothelial protein C receptor (EPCR) blockade activity. Cysteine-rich interdomain regions (CIDRα1) of DC8 and DC13 were expressed and their interactions with EPCR were investigated. Results indicate each domain interact with EPCR in a distinct manner resulting in different levels of inhibition of the activated protein C (APC)-EPCR interaction. Bio-Layer Interferometry was used to study the binding kinetics of the CIDR-EPCR interaction. A Pall ForteBio Octet QKe instrument equipped with biotinylated EPCR captured Streptavidin biosensor probes were used in these assays to determine relevant kinetic parameters (kon, koff, and KD). Overall results of this investigation reveal a functional heterogeneity in the interaction between P. falciparum and EPCR, which would help in the development of novel treatment methods for cerebral malaria.

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