Distinct regions that control ion selectivity and calcium-dependent activation in the bestrophin ion channel.

ABSTRACT: Cytoplasmic calcium (Ca²⁺) activates the bestrophin anion channel, allowing chloride ions to flow down their electrochemical gradient. Mutations in bestrophin 1 (BEST1) cause macular degenerative disorders. Previously, we determined an X-ray structure of chicken BEST1 that revealed the architecture of the channel. Here, we present electrophysiological studies of purified wild-type and mutant BEST1 channels and an X-ray structure of a Ca²⁺-independent mutant. From these experiments, we identify regions of BEST1 responsible for Ca²⁺ activation and ion selectivity. A "Ca²⁺ clasp" within the channel's intracellular region acts as a sensor of cytoplasmic Ca²⁺. Alanine substitutions within a hydrophobic "neck" of the pore, which widen it, ca

SUBMITTER: Vaisey G 

PROVIDER: S-EPMC5127342 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature