Cys-loop receptors constitute a superfamily of pentameric ligand-gated ion channels
(pLGICs), including receptors for acetylcholine, serotonin, glycine and γ-aminobutyric acid.
Several bacterial homologues have been identified that are excellent models for
understanding allosteric binding of alcohols and anesthetics in human Cys-loop receptors.
Recently, we showed that a single point mutation on a prokaryotic homologue (GLIC) could
transform it from a channel weakly potentiated by ethanol into a highly ethanol-sensitive …

Despite high sequence identity, pentameric ligand-gated ion channels exhibit remarkable
diversity in function with anionic/cationic channels that are either potentiated or inhibited by
allosteric ligands. The recently available structures of bacterial homologs of Cys-loop
receptors provide an excellent framework for understanding this allosteric modulation and
function, but the modeling can be complex; our earlier simulations of the prokaryotic anionic
glycine receptor (GlyR) suggest inter-subunit binding for ethanol (Murail, Biophys J 100 …