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Author Spotlight: Identifying Compensatory Pathways in Malaria Parasites Containing Hypomorphic Allele of Essential Protein Kinases
Published on: November 22, 2024
Endogenous structure of antimalarial target PfATP4 reveals an apicomplexan-specific P-type ATPase modulator
Meseret T Haile1, Anurag Shukla2, James Zhen1
1Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA.
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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