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Structural basis for pH gating of the two-pore domain K+ channel TASK2

Author

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  • Baobin Li

    (University of California Berkeley
    University of California Berkeley
    University of California Berkeley)

  • Robert A. Rietmeijer

    (University of California Berkeley
    University of California Berkeley
    University of California Berkeley
    University of California Berkeley)

  • Stephen G. Brohawn

    (University of California Berkeley
    University of California Berkeley
    University of California Berkeley)

Abstract

TASK2 (also known as KCNK5) channels generate pH-gated leak-type K+ currents to control cellular electrical excitability1–3. TASK2 is involved in the regulation of breathing by chemosensory neurons of the retrotrapezoid nucleus in the brainstem4–6 and pH homeostasis by kidney proximal tubule cells7,8. These roles depend on channel activation by intracellular and extracellular alkalization3,8,9, but the mechanistic basis for TASK2 gating by pH is unknown. Here we present cryo-electron microscopy structures of Mus musculus TASK2 in lipid nanodiscs in open and closed conformations. We identify two gates, distinct from previously observed K+ channel gates, controlled by stimuli on either side of the membrane. Intracellular gating involves lysine protonation on inner helices and the formation of a protein seal between the cytoplasm and the channel. Extracellular gating involves arginine protonation on the channel surface and correlated conformational changes that displace the K+-selectivity filter to render it nonconductive. These results explain how internal and external protons control intracellular and selectivity filter gates to modulate TASK2 activity.

Suggested Citation

  • Baobin Li & Robert A. Rietmeijer & Stephen G. Brohawn, 2020. "Structural basis for pH gating of the two-pore domain K+ channel TASK2," Nature, Nature, vol. 586(7829), pages 457-462, October.
    • Handle: RePEc:nat:nature:v:586:y:2020:i:7829:d:10.1038_s41586-020-2770-2
    DOI: 10.1038/s41586-020-2770-2
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    Cited by:

    1. Berke Türkaydin & Marcus Schewe & Elena Barbara Riel & Friederike Schulz & Johann Biedermann & Thomas Baukrowitz & Han Sun, 2024. "Atomistic mechanism of coupling between cytosolic sensor domain and selectivity filter in TREK K2P channels," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Toby S. Turney & Vivian Li & Stephen G. Brohawn, 2022. "Structural Basis for pH-gating of the K+ channel TWIK1 at the selectivity filter," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    3. Marcos Matamoros & Xue Wen Ng & Joshua B. Brettmann & David W. Piston & Colin G. Nichols, 2023. "Conformational plasticity of NaK2K and TREK2 potassium channel selectivity filters," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    4. Franck C. Chatelain & Nicolas Gilbert & Delphine Bichet & Annaïse Jauch & Sylvain Feliciangeli & Florian Lesage & Olivier Bignucolo, 2024. "Mechanistic basis of the dynamic response of TWIK1 ionic selectivity to pH," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    5. Lea C. Neelsen & Elena B. Riel & Susanne Rinné & Freya-Rebecca Schmid & Björn C. Jürs & Mauricio Bedoya & Jan P. Langer & Bisher Eymsh & Aytug K. Kiper & Sönke Cordeiro & Niels Decher & Thomas Baukrow, 2024. "Ion occupancy of the selectivity filter controls opening of a cytoplasmic gate in the K2P channel TALK-2," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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