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A hydrophobic barrier deep within the inner pore of the TWIK-1 K2P potassium channel

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  • Prafulla Aryal

    (Clarendon Laboratory, University of Oxford
    University of Oxford
    OXION Initiative in Ion Channels and Disease, University of Oxford)

  • Firdaus Abd-Wahab

    (Clarendon Laboratory, University of Oxford)

  • Giovanna Bucci

    (Clarendon Laboratory, University of Oxford)

  • Mark S. P. Sansom

    (University of Oxford
    OXION Initiative in Ion Channels and Disease, University of Oxford)

  • Stephen J. Tucker

    (Clarendon Laboratory, University of Oxford
    OXION Initiative in Ion Channels and Disease, University of Oxford)

Abstract

Recent X-ray crystal structures of the two-pore domain (K2P) family of potassium channels have revealed a unique structural architecture at the point where the cytoplasmic bundle-crossing gate is found in most other tetrameric K+ channels. However, despite the apparently open nature of the inner pore in the TWIK-1 (K2P1/KCNK1) crystal structure, the reasons underlying its low levels of functional activity remain unclear. In this study, we use a combination of molecular dynamics simulations and functional validation to demonstrate that TWIK-1 possesses a hydrophobic barrier deep within the inner pore, and that stochastic dewetting of this hydrophobic constriction acts as a major barrier to ion conduction. These results not only provide an important insight into the mechanisms which control TWIK-1 channel activity, but also have important implications for our understanding of how ion permeation may be controlled in similar ion channels and pores.

Suggested Citation

  • Prafulla Aryal & Firdaus Abd-Wahab & Giovanna Bucci & Mark S. P. Sansom & Stephen J. Tucker, 2014. "A hydrophobic barrier deep within the inner pore of the TWIK-1 K2P potassium channel," Nature Communications, Nature, vol. 5(1), pages 1-9, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5377
    DOI: 10.1038/ncomms5377
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    Cited by:

    1. Karin E. J. Rödström & Alexander Cloake & Janina Sörmann & Agnese Baronina & Kathryn H. M. Smith & Ashley C. W. Pike & Jackie Ang & Peter Proks & Marcus Schewe & Ingelise Holland-Kaye & Simon R. Bushe, 2024. "Extracellular modulation of TREK-2 activity with nanobodies provides insight into the mechanisms of K2P channel regulation," Nature Communications, Nature, vol. 15(1), pages 1-13, 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. Ruo-Xu Gu & Bert L. Groot, 2023. "Central cavity dehydration as a gating mechanism of potassium channels," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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