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Conformational plasticity of NaK2K and TREK2 potassium channel selectivity filters

Author

Listed:
  • Marcos Matamoros

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Xue Wen Ng

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Joshua B. Brettmann

    (Washington University School of Medicine
    Millipore-Sigma Inc.)

  • David W. Piston

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Colin G. Nichols

    (Washington University School of Medicine
    Washington University School of Medicine)

Abstract

The K+ channel selectivity filter (SF) is defined by TxGYG amino acid sequences that generate four identical K+ binding sites (S1-S4). Only two sites (S3, S4) are present in the non-selective bacterial NaK channel, but a four-site K+-selective SF is obtained by mutating the wild-type TVGDGN SF sequence to a canonical K+ channel TVGYGD sequence (NaK2K mutant). Using single molecule FRET (smFRET), we show that the SF of NaK2K, but not of non-selective NaK, is ion-dependent, with the constricted SF configuration stabilized in high K+ conditions. Patch-clamp electrophysiology and non-canonical fluorescent amino acid incorporation show that NaK2K selectivity is reduced by crosslinking to limit SF conformational movement. Finally, the eukaryotic K+ channel TREK2 SF exhibits essentially identical smFRET-reported ion-dependent conformations as in prokaryotic K+ channels. Our results establish the generality of K+-induced SF conformational stability across the K+ channel superfamily, and introduce an approach to study manipulation of channel selectivity.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-022-35756-7
    DOI: 10.1038/s41467-022-35756-7
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