Backbone amides are determinants of Cl^- selectivity in CLC ion channels.

ABSTRACT: Chloride homeostasis is regulated in all cellular compartments. CLC-type channels selectively transport Cl^- across biological membranes. It is proposed that side-chains of pore-lining residues determine Cl^- selectivity in CLC-type channels, but their spatial orientation and contributions to selectivity are not conserved. This suggests a possible role for mainchain amides in selectivity. We use nonsense suppression to insert α-hydroxy acids at pore-lining positions in two CLC-type channels, CLC-0 and bCLC-k, thus exchanging peptide-bond amides with ester-bond oxygens which are incapable of hydrogen-bonding. Backbone substitutions functionally degrade inter-anion discrimination in a site-specific manner. The presence of a pore-occupying glutamate side chain modulates th

SUBMITTER: Leisle L 

PROVIDER: S-EPMC9726985 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature