Endogenous structure of antimalarial target PfATP4 reveals an apicomplexan-specific P-type ATPase modulator
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.
Authors
- Joanne M. Morrisey
- Anurag Shukla (ORCID: https://orcid.org/0000-0003-4035-2978)
- Michael W. Mather (ORCID: https://orcid.org/0000-0002-1062-0137)
- Suyash Bhatnagar
- Chi-Min Ho (ORCID: https://orcid.org/0000-0003-2132-7320)
- Akhil B. Vaidya (ORCID: https://orcid.org/0000-0003-1063-5571)
- Z. Zhang
- Meseret T. Haile (ORCID: https://orcid.org/0000-0002-5512-5260)
- James Zhen (ORCID: https://orcid.org/0000-0002-5163-835X)
Institutions
- Columbia University Irving Medical Center (US)
- Drexel University (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-10-20
- DOI
- https://doi.org/10.1038/s41467-025-64815-y
- Primary Topic
- ATP Synthase and ATPases Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- University of South Florida
- National Institutes of Health
- Weill Cornell Medical College