Pentameric ligand-gated ion channels (pLGICs) are a major family of neurotransmitter receptors in the brain and its periphery that encompasses acetyl-choline, serotonine, glycine and γ-amino-butyric acid receptors. All these receptors share a common pentameric architecture with a large extracellular domain (ECD) and a transmembrane domain (TMD) that is composed of four a-helices, named M1 to M4, that form a funnel-shaped pore defined by the M2 helices of each of the subunits. pLGICs are dynamic proteins that couple neurotransmitter binding in the ECD to the opening of the ion channels embedded in their TMD. This coupling involves global conformational reorganisations, thereby generating discrete allosteric states including a basal closed state, an active open state stabilised by agonists and several desensitised closed states. A prerequisite for understanding the gating mechanism of pLGICs at the molecular level is to obtain structural information on each of these different allosteric states.

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