Publication Date:
2014-08-15
Description:
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 A 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 A 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hassaine, Gherici -- Deluz, Cedric -- Grasso, Luigino -- Wyss, Romain -- Tol, Menno B -- Hovius, Ruud -- Graff, Alexandra -- Stahlberg, Henning -- Tomizaki, Takashi -- Desmyter, Aline -- Moreau, Christophe -- Li, Xiao-Dan -- Poitevin, Frederic -- Vogel, Horst -- Nury, Hugues -- England -- Nature. 2014 Aug 21;512(7514):276-81. doi: 10.1038/nature13552. Epub 2014 Aug 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, Switzerland [2] [3] Theranyx, 163 Avenue de Luminy, 13288 Marseille, France. ; 1] Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, Switzerland [2]. ; Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, Switzerland. ; Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel, CH-4058 Basel, Switzerland. ; Swiss Light Source, Paul Scherrer Institute, CH-5234 Villigen, Switzerland. ; Architecture et Fonction des Macromolecules Biologiques, CNRS UMR 7257 and Universite Aix-Marseille, F-13288 Marseille, France. ; 1] Universite Grenoble Alpes, IBS, F-38000 Grenoble, France [2] CNRS, IBS, F-38000 Grenoble, France [3] CEA, DSV, IBS, F-38000 Grenoble, France. ; Laboratory of Biomolecular Research, Paul Scherrer Institute, CH-5232 Villigen, Switzerland. ; Unite de Dynamique Structurale des Macromolecules, Institut Pasteur, CNRS UMR3528, F-75015 Paris, France. ; 1] Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, Switzerland [2] Universite Grenoble Alpes, IBS, F-38000 Grenoble, France [3] CNRS, IBS, F-38000 Grenoble, France [4] CEA, DSV, IBS, F-38000 Grenoble, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25119048" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Animals
;
Binding Sites
;
Crystallography, X-Ray
;
Mice
;
Models, Molecular
;
Molecular Sequence Data
;
Neurotransmitter Agents/metabolism
;
Protein Structure, Quaternary
;
Protein Structure, Tertiary
;
Protein Subunits/chemistry/metabolism
;
Receptors, Serotonin, 5-HT3/*chemistry/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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