Fig. 2: PfATP6 mediates transport of SC83288. | Nature Communications

Fig. 2: PfATP6 mediates transport of SC83288.

From: Mechanisms of PfDNMT2 inhibition and PfATP6-mediated resistance to the antimalarial candidate SC83288 in Plasmodium falciparum

Fig. 2: PfATP6 mediates transport of SC83288.

a Schematic illustration of the experimental strategy to test SC83288 transport by PfATP6. The Saccharomyces cerevisiae K667 strain was complemented with either wild-type PfATP6 or the mutant variant PfATP6F972Y. Endoplasmic reticulum–derived vesicles containing PfATP6 were isolated and tested for uptake of [³H]-SC83288. Generated in Biorender: https://BioRender.com/knyyacx. b Complementation of the Ca2+-sensitive yeast strain K667 by wild type PfATP6 and PfATP6F972Y. Growth was assessed on rich medium (YPD) and synthetic defined (SD) medium lacking uracil (ura) and supplemented with 100 mM or 125 mM CaCl₂. The uracil-auxotrophic, Ca²⁺-resilient strain K607 served as control. c Uptake of [³H]-SC83288 into yeast vesicles containing PfATP6 variants. Vesicles were incubated for 15 min at 30 °C in buffer containing 100 nM [³H]-SC83288 in the presence or absence of ATP (1 mM), CaCl₂ (10 µM), cyclopiazonic acid (CPA; 30 µM), or NP-40 (0.1%). Each point represents an independent biological replicate (n = number of replicates); box plots show median (black line), mean (red line) and interquartile range. The error bars above and below the box indicate the 90th and 10th percentiles. Statistical significance determined by Kruskal–Wallis ANOVA on ranks with Dunn’s post hoc test (black; two-sided; Bonferroni adjusted) and a targeted two-sided t-test for conditions 2 vs 7 (gray). p-values are shown. Source data are provided as a Source Data file.

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