title: X-ray structure of the mouse serotonin 5-HT3 receptor.
abstract: Neurotransmitter-gated ion channels of the Cys-loop receptor family mediate fast neurotransmission throughout the nervous system. The molecular processes of neurotransmitter binding, subsequent opening of the ion channel and ion permeation remain poorly understood. Here we present the X-ray structure of a mammalian Cys-loop receptor, the mouse serotonin 5-HT3 receptor, at 3.5 Å resolution. The structure of the proteolysed receptor, made up of two fragments and comprising part of the intracellular domain, was determined in complex with stabilizing nanobodies. The extracellular domain reveals the detailed anatomy of the neurotransmitter binding site capped by a nanobody. The membrane domain delimits an aqueous pore with a 4.6 Å constriction. In the intracellular domain, a bundle of five intracellular helices creates a closed vestibule where lateral portals are obstructed by loops. This 5-HT3 receptor structure, revealing part of the intracellular domain, expands the structural basis for understanding the operating mechanism of mammalian Cys-loop receptors.
authors.affiliation: 1] Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland [2] [3] Theranyx, 163 Avenue de Luminy, 13288 Marseille, France.
authors.forename: Ghérici
authors.initials: G
authors.lastname: Hassaine
authors.affiliation: 1] Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland [2].
authors.forename: Cédric
authors.initials: C
authors.lastname: Deluz
authors.affiliation: Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: Luigino
authors.initials: L
authors.lastname: Grasso
authors.affiliation: Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: Romain
authors.initials: R
authors.lastname: Wyss
authors.affiliation: Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: Menno B
authors.initials: MB
authors.lastname: Tol
authors.affiliation: Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: Ruud
authors.initials: R
authors.lastname: Hovius
authors.affiliation: Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel, CH-4058 Basel, Switzerland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Graff
authors.affiliation: Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel, CH-4058 Basel, Switzerland.
authors.forename: Henning
authors.initials: H
authors.lastname: Stahlberg
authors.affiliation: Swiss Light Source, Paul Scherrer Institute, CH-5234 Villigen, Switzerland.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tomizaki
authors.affiliation: Architecture et Fonction des Macromolécules Biologiques, CNRS UMR 7257 and Université Aix-Marseille, F-13288 Marseille, France.
authors.forename: Aline
authors.initials: A
authors.lastname: Desmyter
authors.affiliation: 1] Université Grenoble Alpes, IBS, F-38000 Grenoble, France [2] CNRS, IBS, F-38000 Grenoble, France [3] CEA, DSV, IBS, F-38000 Grenoble, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Moreau
authors.affiliation: Laboratory of Biomolecular Research, Paul Scherrer Institute, CH-5232 Villigen, Switzerland.
authors.forename: Xiao-Dan
authors.initials: XD
authors.lastname: Li
authors.affiliation: Unité de Dynamique Structurale des Macromolécules, Institut Pasteur, CNRS UMR3528, F-75015 Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Poitevin
authors.affiliation: Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: Horst
authors.initials: H
authors.lastname: Vogel
authors.affiliation: 1] Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland [2] Université Grenoble Alpes, IBS, F-38000 Grenoble, France [3] CNRS, IBS, F-38000 Grenoble, France [4] CEA, DSV, IBS, F-38000 Grenoble, France.
authors.forename: Hugues
authors.initials: H
authors.lastname: Nury
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018377:Neurotransmitter Agents / Q000378:metabolism; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000737:chemistry* / Q000378:metabolism
chemical_list: D018377:Neurotransmitter Agents; D021122:Protein Subunits; D044406:Receptors, Serotonin, 5-HT3