Characterization of the ATP4 ion pump in Toxoplasma gondii
Adele M Lehane, Adelaide SM Dennis, Katherine O Bray, Dongdi Li, Esther Rajendran, James M McCoy, Hillary M McArthur, Markus Winterberg, Farid Rahimi, Christopher J Tonkin, Kiaran Kirk, Giel G van Dooren
JOURNAL OF BIOLOGICAL CHEMISTRY | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2019
The Plasmodium falciparum ATPase PfATP4 is the target of a diverse range of antimalarial compounds, including the clinical drug candidate cipargamin. PfATP4 was originally annotated as a Ca2+ transporter, but recent evidence suggests that it is a Na+ efflux pump, extruding Na+ in exchange for H+ Here we demonstrate that ATP4 proteins belong to a clade of P-type ATPases that are restricted to apicomplexans and their closest relatives. We employed a variety of genetic and physiological approaches to investigate the ATP4 protein of the apicomplexan Toxoplasma gondii, TgATP4. We show that TgATP4 is a plasma membrane protein. Knockdown of TgATP4 had no effect on resting pH or Ca2+ but rendered pa..View full abstract
Awarded by National Health and Medical Research Council
Awarded by Australian Research Council
This work was supported by National Health and Medical Research Council Grant 1042272 (to K. K.) and Australian Research Council Discovery Project Grant DP150102883 (to K. K. and G. G. v. D.), Linkage Project Grant LP150101226 (to K. K.), Discovery Early Career Researcher Award DE160101035 (to A. M. L.), QEII Fellowship DP110103144 (to G. G. v. D.), and Future Fellowship FT120100164 (to C. J. T.). C. J. T. is grateful for institutional support from the Victorian State Government Operational Infrastructure Support Program and the National Health and Medical Research Council Independent Research Institute Infrastructure Support Scheme. The authors declare that they have no conflicts of interest with the contents of this article.