Figure 1. DHA targets PfPI3K.
a, SS-EEA1WT-mCherry detects ring PI3P in punctate (ER) domains11. Mutant SS-EEA1R1374A-mCherry secretes to the PV (second row; 11). 4 nM DHA redistributes SS-EEA1WT-mCherry to the PV. Washout restores ER-PI3P. 4 nM deoxyartemisinin, no effect. Blue, nucleus; scale, 5 μm; P, parasite; E, Erythrocyte. Mean (SD) with three experimental replicates with image analysis from 400 optical sections. b-d, Effects of DHA on (b) PI3P mass (c) immunopurified PfPI3K (raw data in Supplementary Data 2) and (d) mammalian PI3Kinases. Mean from three experimental replicates (each with triplicate data points). For (b), SD < 3; (c) upper graph, SD < 1.5; lower graph SD < 5; (d) SD < 0.5. e, Overlay of the model of PfPI3K (cyan) and human class III PI3K VPS34 (grey, pdb code 3IHY) with active site marked (asterisk). f, DHA in PfPI3K model (cyan) binding site. g, Surface representation of f. Additional details in Extended Data Figs. 1–3.
