Molecular mechanisms of gating in the calcium-activated chloride channel bestrophin.

ABSTRACT: Bestrophin (BEST1-4) ligand-gated chloride (Cl^-) channels are activated by calcium (Ca²⁺). Mutation of BEST1 causes retinal disease. Partly because bestrophin channels have no sequence or structural similarity to other ion channels, the molecular mechanisms underlying gating are unknown. Here, we present a series of cryo-electron microscopy structures of chicken BEST1, determined at 3.1 Å resolution or better, that represent the channel's principal gating states. Unlike other channels, opening of the pore is due to the repositioning of tethered pore-lining helices within a surrounding protein shell that dramatically widens a neck of the pore through a concertina of amino acid rearrangements. The neck serves as both the activation and the inactivation gate. Ca^2+</

SUBMITTER: Miller AN 

PROVIDER: S-EPMC6342527 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature