Investigating PI3P Binding with Plasmodium Falciparum HSP70 Proteins

Abstract

aims: Investigating the binding of phosphatidylinositol 3 phosphate (PI3P) with Plasmodium falciparum heat shock protein 70 homologs background: 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 a crucial lipid modulatorPI3P and the C terminal lid domain of cytosolic PfHSP70-1, stabilizes the parasite digestive vacuole (DV) to facilitate hemoglobin trafficking and breakdown in turn impacting parasite survival. PfHSP70 homologs and PI3P are amply expressed together in various subcellular compartments of the parasite providing these with an opportunity to interact and affect biological processes. objective: The objectives of this study included identification of the PI3P binding pockets on PfHSP70s, understanding the binding affinity of each homolog for PI3P and identifying residues involved in different types of interactions. method: We have analyzed PI3P binding of all four PfHSP70s by using bioinformatics tools like sequence analysis, molecular docking and LigPlot+ analysis. result: Our results show that differently localized PfHSP70 homologs bind PI3P with variable affinity. The mitochondrial and ER localized PfHSP70s bind more strongly with PI3P than their cytosolic counterpart PfHSP70-1. The PI3P binding region on all PfHSP70 homologs lies at the interface of helices 1 and 3 of their substrate binding domain . Analysis of these results has also helped to pinpoint specific residues on PfHSP70s that may be engaged in these interactions. conclusion: PI3P preferentially binds to a particular pocket on PfHSP70 homologs. Different PfHSP70s bind to PI3P with variable binding affinity. Specific residues of PfHSP70 homologs involved in these interactions have been identified. other: The present study may therefore form the basis for designing interventions that hinder PfHSP70-PI3P interaction and influence parasite survival.