β subunits of GABA_A receptors form proton-gated chloride channels: Insights into the molecular basis.

ABSTRACT: Gamma-aminobutyric acid type A receptors (GABA_ARs) are ligand gated channels mediating inhibition in the central nervous system. Here, we identify a so far undescribed function of β-subunit homomers as proton-gated anion channels. Mutation of a single H267A in β3 subunits completely abolishes channel activation by protons. In molecular dynamic simulations of the β3 crystal structure protonation of H267 increased the formation of hydrogen bonds between H267 and E270 of the adjacent subunit leading to a pore stabilising ring formation and accumulation of Cl^- within the transmembrane pore. Conversion of these residues in proton insensitive ρ1 subunits transfers proton-dependent gating, thus highlighting the role of this interaction in proton sensitivity. Activation of ch

SUBMITTER: Garifulina A 

PROVIDER: S-EPMC9349252 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature