Cryo-EM structures of a pentameric ligand-gated ion channel in liposomes.

ABSTRACT: Detergents and lipid nanodiscs affect the cryo-EM structures of pentameric ligand-gated ion channels (pLGICs) including ELIC. To determine the structure of a pLGIC in a membrane environment that supports ion channel function, we performed single particle cryo-EM of ELIC in liposomes. ELIC activation and desensitization were confirmed in liposomes with a stopped-flow thallium flux assay. Using WT ELIC and a non-desensitizing mutant (ELIC5), we captured resting, activated and desensitized structures at high resolution. In the desensitized structure, the ion conduction pore has a constriction at the 9' leucine of the pore-lining M2 helix, indicating that 9' is the desensitization gate in ELIC. The agonist-bound structures of ELIC in liposomes are distinct from those in nanodiscs. In general,

SUBMITTER: Dalal V 

PROVIDER: S-EPMC12157481 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature