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Electromechanical coupling in the hyperpolarization-activated K+ channel KAT1

Author

Listed:
  • Michael David Clark

    (The University of Chicago)

  • Gustavo F. Contreras

    (The University of Chicago)

  • Rong Shen

    (The University of Chicago)

  • Eduardo Perozo

    (The University of Chicago)

Abstract

Voltage-gated potassium (Kv) channels coordinate electrical signalling and control cell volume by gating in response to membrane depolarization or hyperpolarization. However, although voltage-sensing domains transduce transmembrane electric field changes by a common mechanism involving the outward or inward translocation of gating charges1–3, the general determinants of channel gating polarity remain poorly understood4. Here we suggest a molecular mechanism for electromechanical coupling and gating polarity in non-domain-swapped Kv channels on the basis of the cryo-electron microscopy structure of KAT1, the hyperpolarization-activated Kv channel from Arabidopsis thaliana. KAT1 displays a depolarized voltage sensor, which interacts with a closed pore domain directly via two interfaces and indirectly via an intercalated phospholipid. Functional evaluation of KAT1 structure-guided mutants at the sensor–pore interfaces suggests a mechanism in which direct interaction between the sensor and the C-linker hairpin in the adjacent pore subunit is the primary determinant of gating polarity. We suggest that an inward motion of the S4 sensor helix of approximately 5–7 Å can underlie a direct-coupling mechanism, driving a conformational reorientation of the C-linker and ultimately opening the activation gate formed by the S6 intracellular bundle. This direct-coupling mechanism contrasts with allosteric mechanisms proposed for hyperpolarization-activated cyclic nucleotide-gated channels5, and may represent an unexpected link between depolarization- and hyperpolarization-activated channels.

Suggested Citation

  • Michael David Clark & Gustavo F. Contreras & Rong Shen & Eduardo Perozo, 2020. "Electromechanical coupling in the hyperpolarization-activated K+ channel KAT1," Nature, Nature, vol. 583(7814), pages 145-149, July.
  • Handle: RePEc:nat:nature:v:583:y:2020:i:7814:d:10.1038_s41586-020-2335-4
    DOI: 10.1038/s41586-020-2335-4
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    Citations

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    Cited by:

    1. Yaming Lu & Miao Yu & Yutian Jia & Fan Yang & Yanming Zhang & Xia Xu & Xiaomin Li & Fan Yang & Jianlin Lei & Yi Wang & Guanghui Yang, 2022. "Structural basis for the activity regulation of a potassium channel AKT1 from Arabidopsis," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Verena Burtscher & Jonathan Mount & Jian Huang & John Cowgill & Yongchang Chang & Kathleen Bickel & Jianhan Chen & Peng Yuan & Baron Chanda, 2024. "Structural basis for hyperpolarization-dependent opening of human HCN1 channel," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. Mingfeng Zhang & Yuanyue Shan & Duanqing Pei, 2023. "Mechanism underlying delayed rectifying in human voltage-mediated activation Eag2 channel," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    4. Carlos A. Z. Bassetto & Flavio Costa & Carlo Guardiani & Francisco Bezanilla & Alberto Giacomello, 2023. "Noncanonical electromechanical coupling paths in cardiac hERG potassium channel," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

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