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

Gherici Hassaine, Cedric Deluz, Luigino Grasso, Romain Wyss, Menno B. Tol, Ruud Hovius, Alexandra Graff, Henning Stahlberg, Takashi Tomizaki, Aline Desmyter, Christophe Moreau, Xiao-Dan Li, Frederic Poitevin, Horst Vogel, Hugues Nury*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

272 Citations (Scopus)

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 angstrom 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 angstrom 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.

Original languageEnglish
Pages (from-to)276-+
Number of pages21
JournalNature
Volume512
Issue number7514
DOIs
Publication statusPublished - 21-Aug-2014
Externally publishedYes

Keywords

  • GATED ION-CHANNEL
  • NICOTINIC ACETYLCHOLINE-RECEPTOR
  • LIGAND-BINDING DOMAIN
  • CYS-LOOP RECEPTORS
  • SELECTIVITY-FILTER
  • 5-HT(3)A RECEPTOR
  • MAMMALIAN-CELLS
  • AGONIST BINDING
  • PERMEATION
  • PORE

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