Assembly and cooperative mechanism of the hexameric fungal plasma membrane H+-ATPase

The fungal plasma membrane H+-ATPase Pma1 hydrolyzes ATP to pump protons out of the cell to maintain the intracellular pH and membrane potential. Pma1 is unique among the P-type ATPases as it functions as a hexamer, although the underlying mechanism has been unclear. Here, we show that the Pma1 hexamer functions cooperatively, and the cooperativity is mediated by the domain-swapped N-terminal extension (NTE). The NTE of one Pma1 subunit binds to the nucleotide-binding domain of a neighboring subunit and, thus, couples the conformational changes of two neighboring subunits, enabling inter-subunit cooperativity of the ATPase activity by the hexamer. We further demonstrate that the NTE is essential for Pma1's cooperative activity and physiological function. Therefore, our work suggests that Pma1 assembles a hexamer to promote a more efficient proton-pumping activity, perhaps to rapidly respond to environmental changes, and may facilitate antifungal drug development targeting Pma1.

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Publication Details

Journal
Cell Reports
Published
2025-05-24
DOI
https://doi.org/10.1016/j.celrep.2025.115753
Citations
3
Primary Topic
ATP Synthase and ATPases Research
Type
article
Field-Weighted Citation Impact
2.42

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article

Assembly and cooperative mechanism of the hexameric fungal plasma membrane H+-ATPase

Cai‐Hong Yun, Yu‐Cheng Gu, Kuize Liu, Lin Bai et al.
3 citations
Cell Reports
ATP Synthase and ATPases Research
2.42
article

Assembly and cooperative mechanism of the hexameric fungal plasma membrane H+-ATPase

Cai‐Hong Yun, Yu‐Cheng Gu, Kuize Liu, Lin Bai, Yinggai Song, Zi-Long You, Le-Xuan Wang, Peng Zhao, Lin Wang, Dandan Chen, Kai Wang, Hua Li, Yong Ni, Pengyan Xia, Chaoran Zhao
article en
3 citations

Abstract

The fungal plasma membrane H+-ATPase Pma1 hydrolyzes ATP to pump protons out of the cell to maintain the intracellular pH and membrane potential. Pma1 is unique among the P-type ATPases as it functions as a hexamer, although the underlying mechanism has been unclear. Here, we show that the Pma1 hexamer functions cooperatively, and the cooperativity is mediated by the domain-swapped N-terminal extension (NTE). The NTE of one Pma1 subunit binds to the nucleotide-binding domain of a neighboring subunit and, thus, couples the conformational changes of two neighboring subunits, enabling inter-subunit cooperativity of the ATPase activity by the hexamer. We further demonstrate that the NTE is essential for Pma1's cooperative activity and physiological function. Therefore, our work suggests that Pma1 assembles a hexamer to promote a more efficient proton-pumping activity, perhaps to rapidly respond to environmental changes, and may facilitate antifungal drug development targeting Pma1.

Cell ReportsVol. 44(6)
Beijing Tongren Hospital (CN), Peking University (CN), Sichuan University (CN), Syngenta (United Kingdom) (GB), Peking University First Hospital (CN)
National Natural Science Foundation of China, Natural Science Foundation of Beijing Municipality, Peking University
Openalex Percentile: Top 12%
ATP Synthase and ATPases Research
2.42
DOIOpen Access PDFOpenAlex
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