Conformational plasticity of NaK2K and TREK2 potassium channel selectivity filters
Nature communications(2023)
摘要
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.
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关键词
Ion transport,Permeation and transport,Potassium channels,Science,Humanities and Social Sciences,multidisciplinary
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