Investigating the PI3P binding pockets of Plasmodium falciparum HSP70 proteins

Abstract The 70 kDa Plasmodium falciparum (Pf) heat shock proteins (PfHSP70s) are an important class of molecules that are critically involved in parasite survival through periods of stress. Interaction between the cytosolic PfHSP70-1 and a crucial lipid modulator, phosphatidylinositol 3 phosphate (PI3P) stabilizes the parasite digestive vacuole (DV) to facilitate haemoglobin trafficking and breakdown in turn impacting parasite survival. The PI3P binding region on PfHSP70-1 is hosted by its C-terminal LID domain that controls substrate binding. Lipidic regulator ‘PI3P’ and PfHSP70 homologs are amply expressed together in various subcellular compartments of the parasite providing these with an opportunity to interact and affect biological processes. Here, we have identified and analysed the PI3P binding pockets of all four PfHSP70s by using structural bioinformatics tools in an attempt to understand their interaction with this lipid. Our results show that differently localized PfHSP70 homologs bind PI3P with variable affinity. Analysis of these results has also helped to pinpoint specific residues on PfHSP70s that may be engaged in these interactions. The present study may therefore form the basis for designing interventions that hinder PfHSP70-PI3P interaction and influence parasite survival.