Differential ion dehydration energetics explains selectivity in the non-canonical lysosomal K⁺ channel TMEM175.

ABSTRACT: Structures of the human lysosomal K⁺ channel transmembrane protein 175 (TMEM175) in open and closed states revealed a novel architecture lacking the canonical K⁺ selectivity filter motif present in previously known K⁺ channel structures. A hydrophobic constriction composed of four isoleucine residues was resolved in the pore and proposed to serve as the gate in the closed state, and to confer ion selectivity in the open state. Here, we achieve higher-resolution structures of the open and closed states and employ molecular dynamics simulations to analyze the conducting properties of the putative open state, demonstrating that it is permeable to K⁺ and, to a lesser degree, also Na⁺. Both cations must dehydrate significantly to penetrate

SUBMITTER: Oh S 

PROVIDER: S-EPMC9129878 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature