Expression and functional characterization of a Plasmodium falciparum Ca2+-ATPase (PfATP4) belonging to a subclass unique to apicomplexan organisms

Krishna, S., Woodrow, C., Webb, R., Penny, J., Takeyasu, K., Kimura, M. and East, J.M. (2001) Expression and functional characterization of a Plasmodium falciparum Ca2+-ATPase (PfATP4) belonging to a subclass unique to apicomplexan organisms. The Journal of Biological Chemistry, 276 (14), 10782-10787. (doi:10.1074/jbc.M010554200).

Abstract

We have obtained a full-length P type ATPase sequence (PfATP4) encoded by Plasmodium falciparum and expressed PfATP4 in Xenopus laevis oocytes to study its function. Comparison of the hitherto incomplete open reading frame with other Ca2+-ATPase sequences reveals that PfATP4 differs significantly from previously defined categories. The Ca2+-dependent ATPase activity of PfATP4 is stimulated by a much broader range of [Ca2+]free (3.2-320 µM) than are an avian SERCA1 pump or rabbit SERCA 1a (maximal activity < 10 µM). The activity of PfATP4 is resistant to inhibition by ouabain (200 µM) or thapsigargin (0.8 µM) but is inhibited by vanadate (1 mM) or cyclopiazonic acid (1 µM). We used a quantitative polymerase chain reaction to assay expression of mRNA encoding PfATP4 relative to that for -tubulin in synchronized asexual stages and found variable expression throughout the life cycle with a maximal 5-fold increase in meronts compared with ring stages. This analysis suggests that PfATP4 defines a novel subclass of Ca2+-ATPases unique to apicomplexan organisms and therefore offers potential as a drug target.

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