Gating the pore of the calcium-activated chloride channel TMEM16A.

ABSTRACT: The binding of cytoplasmic Ca²⁺ to the anion-selective channel TMEM16A triggers a conformational change around its binding site that is coupled to the release of a gate at the constricted neck of an hourglass-shaped pore. By combining mutagenesis, electrophysiology, and cryo-electron microscopy, we identified three hydrophobic residues at the intracellular entrance of the neck as constituents of this gate. Mutation of each of these residues increases the potency of Ca²⁺ and results in pronounced basal activity. The structure of an activating mutant shows a conformational change of an α-helix that contributes to Ca²⁺ binding as a likely cause for the basal activity. Although not in physical contact, the three residues are functionally coupled to collectively

SUBMITTER: Lam AKM 

PROVIDER: S-EPMC7862301 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature