Allosteric Cholesterol Site in Glycine Receptors Characterized through Molecular Simulations.

ABSTRACT: Glycine receptors are pentameric ligand-gated ion channels that conduct chloride ions across postsynaptic membranes to facilitate fast inhibitory neurotransmission. In addition to gating by the glycine agonist, interactions with lipids and other compounds in the surrounding membrane environment modulate their function, but molecular details of these interactions remain unclear, in particular, for cholesterol. Here, we report coarse-grained simulations in a model neuronal membrane for three zebrafish glycine receptor structures representing apparent resting, open, and desensitized states. We then converted the systems to all-atom models to examine detailed lipid interactions. Cholesterol bound to the receptor at an outer-leaflet intersubunit site, with a preference for the open and desensit

SUBMITTER: Jalalypour F 

PROVIDER: S-EPMC11129184 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature