Structures and gating mechanisms of human bestrophin anion channels.

ABSTRACT: Bestrophin-1 (Best1) and bestrophin-2 (Best2) are two members of the bestrophin family of calcium (Ca²⁺)-activated chloride (Cl^-) channels with critical involvement in ocular physiology and direct pathological relevance. Here, we report cryo-EM structures of wild-type human Best1 and Best2 in various states at up to 1.8 Å resolution. Ca²⁺-bound Best1 structures illustrate partially open conformations at the two Ca²⁺-dependent gates of the channels, in contrast to the fully open conformations observed in Ca²⁺-bound Best2, which is in accord with the significantly smaller currents conducted by Best1 in electrophysiological recordings. Comparison of the closed and open states reveals a C-terminal auto-inhibitory segment (AS), which constr

SUBMITTER: Owji AP 

PROVIDER: S-EPMC9253114 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature