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AI-guided discovery of a novel ATP/ADP binding domain in plant HAK transporters that regulates K+/Na+ homeostasis

This article is a preprint and has not been certified by peer review.

Authors

    Fan Yang,  
    Fan Yang
    • China Agricultural University
    Qinrui Wang,  
    Qinrui Wang
    • DP technology
    Junzhao Yang,  
    Junzhao Yang
    • China Agricultural University
    Ruoxian Xia,  
    Ruoxian Xia
    • China Agricultural University
    Yaming Lu,  
    Yaming Lu
    • China Agricultural University
    Xia Xu,  
    Xia Xu
    • China Agricultural University
    Peng Fu,  
    Peng Fu
    • China Agricultural University
    Jiaqi Zhou,  
    Jiaqi Zhou
    • China Agricultural University
    Yutian Jia,  
    Yutian Jia
    • China Agricultural University
    Han Wen,  
    Han Wen
    • Peking University
    Guanghui Yang
    Guanghui Yang
Categories
Biology x AI

Abstract

Maintaining Na+/K+ homeostasis is fundamental for plant environmental adaptation. Using domain classification of plant Na+/K+ transport proteins, and AI-based ligand screening integrated with biochemical characterization, we identified a previously unannotated cytoplasmic domain (CPD) in plant HAKs as a novel ATP/ADP-binding fold. We demonstrate that ATP/ADP binding to the CPD directly couples to the gating of ion transport, a regulatory mechanism previously unknown in this transporter family. Cryo-EM structures of Arabidopsis HAK5 in ADP-bound and ligand-free states, alongside Zea mays HAK4 in an ATP-bound state, revealing a distinctive autoinhibitory mechanism. In the ADP-bound state, the CPD physically obstructs the transmembrane ion pathway. Conversely, the gain-of-function mutant AtHAK5D152A triggers a downward translocation of the CPD to release this inhibition, which is corroborated by the ATP binding conformation of ZmHAK4. Our study defines the structural basis for ATP/ADP- associated gating in plant HAK transporters, providing a novel molecular framework for engineering salt-tolerant crops.

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DOI:

https://doi.org/10.65215/LTSpreprints.2026.04.07.000179

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2026-04-08

How to Cite

Yang, F., Wang, Q., Yang, J., Xia, R., Lu, Y., Xu, X., Fu, P., Zhou, J., Jia, Y., Wen, H., & Yang, G. (2026). AI-guided discovery of a novel ATP/ADP binding domain in plant HAK transporters that regulates K+/Na+ homeostasis. LangTaoSha Preprint Server. https://doi.org/10.65215/LTSpreprints.2026.04.07.000179

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