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A single NaK channel conformation is not enough for non-selective ion conduction

Author

Listed:
  • Chaowei Shi

    (Leibniz-Forschungsinstitut für Molekulare Pharmakologie)

  • Yao He

    (University of Science and Technology of China)

  • Kitty Hendriks

    (Leibniz-Forschungsinstitut für Molekulare Pharmakologie)

  • Bert L. de Groot

    (Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry)

  • Xiaoying Cai

    (University of Science and Technology of China)

  • Changlin Tian

    (University of Science and Technology of China)

  • Adam Lange

    (Leibniz-Forschungsinstitut für Molekulare Pharmakologie
    Humboldt-Universität zu Berlin)

  • Han Sun

    (Section Structural Biology, Leibniz-Forschungsinstitut für Molekulare Pharmakologie)

Abstract

NaK and other non-selective channels are able to conduct both sodium (Na+) and potassium (K+) with equally high efficiency. In contrast to previous crystallographic results, we show that the selectivity filter (SF) of NaK in native-like lipid membranes adopts two distinct conformations that are stabilized by either Na+ or K+ ions. The atomic differences of these conformations are resolved by solid-state NMR (ssNMR) spectroscopy and molecular dynamics (MD) simulations. Besides the canonical K+ permeation pathway, we identify a side entry ion-conduction pathway for Na+ permeation unique to NaK. Moreover, under otherwise identical conditions ssNMR spectra of the K+ selective NaK mutant (NaK2K) reveal only a single conformational state. Therefore, we propose that structural plasticity within the SF and the selection of these conformations by different ions are key molecular determinants for highly efficient conduction of different ions in non-selective cation channels.

Suggested Citation

  • Chaowei Shi & Yao He & Kitty Hendriks & Bert L. de Groot & Xiaoying Cai & Changlin Tian & Adam Lange & Han Sun, 2018. "A single NaK channel conformation is not enough for non-selective ion conduction," Nature Communications, Nature, vol. 9(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03179-y
    DOI: 10.1038/s41467-018-03179-y
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    Cited by:

    1. Rongming Xu & Yuan Kang & Weiming Zhang & Bingcai Pan & Xiwang Zhang, 2023. "Two-dimensional MXene membranes with biomimetic sub-nanochannels for enhanced cation sieving," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    2. Adam Lewis & Vilius Kurauskas & Marco Tonelli & Katherine Henzler-Wildman, 2021. "Ion-dependent structure, dynamics, and allosteric coupling in a non-selective cation channel," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    3. Ahmed Rohaim & Bram J. A. Vermeulen & Jing Li & Felix Kümmerer & Federico Napoli & Lydia Blachowicz & João Medeiros-Silva & Benoît Roux & Markus Weingarth, 2022. "A distinct mechanism of C-type inactivation in the Kv-like KcsA mutant E71V," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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