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Molecular mechanism underlying regulation of Arabidopsis CLCa transporter by nucleotides and phospholipids

Author

Listed:
  • Zhao Yang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Xue Zhang

    (Chinese Academy of Sciences)

  • Shiwei Ye

    (University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Jingtao Zheng

    (Shanghai Normal University)

  • Xiaowei Huang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Fang Yu

    (Shanghai Normal University)

  • Zhenguo Chen

    (Fudan University)

  • Shiqing Cai

    (Chinese Academy of Sciences)

  • Peng Zhang

    (Chinese Academy of Sciences)

Abstract

Chloride channels (CLCs) transport anion across membrane to regulate ion homeostasis and acidification of intracellular organelles, and are divided into anion channels and anion/proton antiporters. Arabidopsis thaliana CLCa (AtCLCa) transporter localizes to the tonoplast which imports NO3− and to a less extent Cl− from cytoplasm. The activity of AtCLCa and many other CLCs is regulated by nucleotides and phospholipids, however, the molecular mechanism remains unclear. Here we determine the cryo-EM structures of AtCLCa bound with NO3− and Cl−, respectively. Both structures are captured in ATP and PI(4,5)P2 bound conformation. Structural and electrophysiological analyses reveal a previously unidentified N-terminal β-hairpin that is stabilized by ATP binding to block the anion transport pathway, thereby inhibiting the AtCLCa activity. While AMP loses the inhibition capacity due to lack of the β/γ- phosphates required for β-hairpin stabilization. This well explains how AtCLCa senses the ATP/AMP status to regulate the physiological nitrogen-carbon balance. Our data further show that PI(4,5)P2 or PI(3,5)P2 binds to the AtCLCa dimer interface and occupies the proton-exit pathway, which may help to understand the inhibition of AtCLCa by phospholipids to facilitate guard cell vacuole acidification and stomatal closure. In a word, our work suggests the regulatory mechanism of AtCLCa by nucleotides and phospholipids under certain physiological scenarios and provides new insights for future study of CLCs.

Suggested Citation

  • Zhao Yang & Xue Zhang & Shiwei Ye & Jingtao Zheng & Xiaowei Huang & Fang Yu & Zhenguo Chen & Shiqing Cai & Peng Zhang, 2023. "Molecular mechanism underlying regulation of Arabidopsis CLCa transporter by nucleotides and phospholipids," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40624-z
    DOI: 10.1038/s41467-023-40624-z
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    References listed on IDEAS

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