Endogenous structure of antimalarial target PfATP4 reveals an apicomplexan-specific P-type ATPase modulator.

Haile, Meseret T; Shukla, Anurag; Zhen, James; Mather, Michael W; Bhatnagar, Suyash; Morrisey, Joanne M; Zhang, Zhening; Vaidya, Akhil B et al. · Nat Commun · 2025

basic_science · Level V

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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 Å 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 an unexplored avenue for designing PfATP4 inhibitors.

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