Conformational plasticity of NaK2K and TREK2 potassium channel selectivity filters

Marcos Matamoros, Xue Wen Ng, Joshua B. Brettmann, David W. Piston and Colin G. Nichols ()
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Marcos Matamoros: Washington University School of Medicine
Xue Wen Ng: Washington University School of Medicine
Joshua B. Brettmann: Washington University School of Medicine
David W. Piston: Washington University School of Medicine
Colin G. Nichols: Washington University School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-022-35756-7

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