Ligand-Gated Pentameric ion Channels, from Binding to Gating

Abstract

X-ray structures of molluscan acetylcholine-binding proteins and procaryotic proton-activated ion channels (ELIC and GLIC) enable us to model the ligand binding and activation mechanism of ligand-gated pentameric ion channels. Common versus distinct features can be deduced from the binding of agonists, antagonists and allosteric modulators in subunit interfaces of nicotinic acetylcholine, A-type γ-aminobutyric acid, glycine and 5-HT3-type serotonin receptors. Ligand interactions in subunit interfaces elicit conformational waves from the closure of the agonist-binding cavity through binding loops, ß-strands and transmembrane helices to pore gating. Keywords: AChBP, pLGIC, nicotinic receptors, GABAA/C receptors, glycine receptors, 5-HT3 receptors, interface binding cavity, binding-gating coupling, allostery, homology modeling