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  Asymmetric opening of the homopentameric 5-HT3A serotonin receptor in lipid bilayers

Zhang, Y., Dijkman, P. M., Zou, R., Zandl-Lang, M., Sanchez, R. M., Eckhardt-Strelau, L., et al. (2021). Asymmetric opening of the homopentameric 5-HT3A serotonin receptor in lipid bilayers. Nature Communications, 12(1): 1074. doi:10.1038/s41467-021-21016-7.

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 Creators:
Zhang, Yingyi1, 2, Author              
Dijkman, Pratricia M.1, 2, Author              
Zou, Rongfeng3, Author
Zandl-Lang, Martina4, Author
Sanchez, Ricardo M.1, 2, Author              
Eckhardt-Strelau, Luise1, Author              
Köfeler, Harald5, Author
Vogel, Horst3, 6, Author
Yuan, Shuguang3, Author
Kudryashev, Mikhail1, Author              
Affiliations:
1Sofja Kovalevskaja Group, Max Planck Institute of Biophysics, Max Planck Society, ou_2253651              
2Buchmann Institute for Molecular Life Sciences (BMLS), Goethe University of Frankfurt, Frankfurt am Main, Germany, ou_persistent22              
3Research Center for Computer-Aided Drug Discovery, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China, ou_persistent22              
4Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria, ou_persistent22              
5Core Facility Mass Spectrometry, ZMF, Medical University of Graz, Graz, Austria, ou_persistent22              
6Institute of Chemical Sciences and Engineering (ISIC), EcolePolytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, ou_persistent22              

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 Abstract: Pentameric ligand-gated ion channels (pLGICs) of the Cys-loop receptor family are key players in fast signal transduction throughout the nervous system. They have been shown to be modulated by the lipid environment, however the underlying mechanism is not well understood. We report three structures of the Cys-loop 5-HT3A serotonin receptor (5HT3R) reconstituted into saposin-based lipid bilayer discs: a symmetric and an asymmetric apo state, and an asymmetric agonist-bound state. In comparison to previously published 5HT3R conformations in detergent, the lipid bilayer stabilises the receptor in a more tightly packed, 'coupled' state, involving a cluster of highly conserved residues. In consequence, the agonist-bound receptor conformation adopts a wide-open pore capable of conducting sodium ions in unbiased molecular dynamics (MD) simulations. Taken together, we provide a structural basis for the modulation of 5HT3R by the membrane environment, and a model for asymmetric activation of the receptor.

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Language(s): eng - English
 Dates: 2020-10-262021-01-062021-02-16
 Publication Status: Published online
 Pages: 15
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41467-021-21016-7
BibTex Citekey: zhang_asymmetric_2021
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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 12 (1) Sequence Number: 1074 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723