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X-ray structure of the mouse serotonin 5-HT3 receptor

Ghérici Hassaine, Cédric Deluz, Luigino Grasso, Romain Wyss, Menno B. Tol, Ruud Hovius, Alexandra Graff, Henning Stahlberg, Takashi Tomizaki, Aline Desmyter, Christophe Moreau, Xiao-Dan Li, Frédéric Poitevin, Horst Vogel () and Hugues Nury ()
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Ghérici Hassaine: Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland
Cédric Deluz: Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland
Luigino Grasso: Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland
Romain Wyss: Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland
Menno B. Tol: Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland
Ruud Hovius: Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland
Alexandra Graff: Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel, CH-4058 Basel, Switzerland
Henning Stahlberg: Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel, CH-4058 Basel, Switzerland
Takashi Tomizaki: Swiss Light Source, Paul Scherrer Institute, CH-5234 Villigen, Switzerland
Aline Desmyter: Architecture et Fonction des Macromolécules Biologiques, CNRS UMR 7257 and Université Aix-Marseille, F-13288 Marseille, France
Christophe Moreau: Université Grenoble Alpes, IBS, F-38000 Grenoble, France
Xiao-Dan Li: Laboratory of Biomolecular Research, Paul Scherrer Institute, CH-5232 Villigen, Switzerland
Frédéric Poitevin: Unité de Dynamique Structurale des Macromolécules, Institut Pasteur, CNRS UMR3528, F-75015 Paris, France
Horst Vogel: Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland
Hugues Nury: Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland

Nature, 2014, vol. 512, issue 7514, 276-281

Abstract: 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.

Date: 2014
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DOI: 10.1038/nature13552

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