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bioRxiv · 10.1101/2025.02.25.640208

Endogenous structure of antimalarial target PfATP4 reveals new class of apicomplexan P-type ATPase modulators

Haile, M. T.·Shukla, A.·Zhen, J.·Mather, M. W.·Bhatnagar, S.·Zhang, Z.·Vaidya, A. B.·Ho, C.-M.
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Abstract

The Plasmodium falciparum sodium efflux pump PfATP4 is a leading antimalarial target, but suffers from a lack of high-resolution structural information needed to identify functionally important features in conserved regions and guide rational design of next generation inhibitors. Here, we determine a 3.7[A] cryoEM structure of PfATP4 purified from CRISPR-engineered P. falciparum parasites, revealing a previously unknown, apicomplexan-specific binding partner, PfABP, which forms a conserved, likely modulatory interaction with PfATP4. The discovery of PfABP presents a new avenue for designing novel PfATP4 inhibitors.

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Haile, M. T., Shukla, A., Zhen, J., Mather, M. W., Bhatnagar, S., Zhang, Z., Vaidya, A. B., Ho, C.-M.. 2025-02-25. Endogenous structure of antimalarial target PfATP4 reveals new class of apicomplexan P-type ATPase modulators. https://doi.org/10.1101/2025.02.25.640208

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