title: Emerging Molecular Mechanisms of Signal Transduction in Pentameric Ligand-Gated Ion Channels.
abstract: Nicotinic acetylcholine, serotonin type 3, γ-amminobutyric acid type A, and glycine receptors are major players of human neuronal communication. They belong to the family of pentameric ligand-gated ion channels, sharing a highly conserved modular 3D structure. Recently, high-resolution structures of both open- and closed-pore conformations have been solved for a bacterial, an invertebrate, and a vertebrate receptor in this family. These data suggest that a common gating mechanism occurs, coupling neurotransmitter binding to pore opening, but they also pinpoint significant differences among subtypes. In this Review, we summarize the structural and functional data in light of these gating models and speculate about their mechanistic consequences on ion permeation, pathological mutations, as well as functional regulation by orthosteric and allosteric effectors.
authors.affiliation: Channel-Receptors Unit, Institut Pasteur, 75015 Paris, France; CNRS UMR 3571, 75015 Paris, France.
authors.forename: Ákos
authors.initials: Á
authors.lastname: Nemecz
authors.affiliation: Institute of Structural and Molecular Biology, University College London and Birkbeck, Malet Street, London WC1E 7HX, UK.
authors.forename: Marie S
authors.initials: MS
authors.lastname: Prevost
authors.affiliation: Channel-Receptors Unit, Institut Pasteur, 75015 Paris, France; CNRS UMR 3571, 75015 Paris, France; Université Pierre et Marie Curie (UPMC), Cellule Pasteur, 75005 Paris, France.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Menny
authors.affiliation: Channel-Receptors Unit, Institut Pasteur, 75015 Paris, France; CNRS UMR 3571, 75015 Paris, France. Electronic address: pjcorrin@pasteur.fr.
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Corringer
mesh_terms: D000818:Animals; D055592:Biophysical Phenomena / Q000502:physiology*; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D058446:Ligand-Gated Ion Channels / Q000378:metabolism*; D008958:Models, Molecular; D018009:Receptors, Glycine / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D058446:Ligand-Gated Ion Channels; D018009:Receptors, Glycine