Repository logo

Infoscience

  • English
  • French
Log In
Logo EPFL, École polytechnique fédérale de Lausanne

Infoscience

  • English
  • French
Log In
  1. Home
  2. Academic and Research Output
  3. Journal articles
  4. Asymmetric opening of the homopentameric 5-HT3A serotonin receptor in lipid bilayers
 
research article

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

Zhang, Yingyi
•
Dijkman, Patricia M.
•
Zou, Rongfeng
Show more
February 16, 2021
Nature Communications

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 (5HT(3)R) 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 5HT(3)R 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 5HT(3)R by the membrane environment, and a model for asymmetric activation of the receptor. Pentameric ligand-gated ion channels (pLGICs) are key players in neurotransmission and have been shown to be modulated by the lipid environment, however the underlying mechanism is not well understood. Here, the authors report structures of the pLGIC 5-HT3A serotonin receptor reconstituted into lipid bilayer discs and reveal lipid-protein interactions as well as asymmetric activation of the homopentameric receptor.

  • Files
  • Details
  • Metrics
Type
research article
DOI
10.1038/s41467-021-21016-7
Web of Science ID

WOS:000626756600012

Author(s)
Zhang, Yingyi
Dijkman, Patricia M.
Zou, Rongfeng
Zandl-Lang, Martina
Sanchez, Ricardo M.
Eckhardt-Strelau, Luise
Kofeler, Harald
Vogel, Horst  
Yuan, Shuguang
Kudryashev, Mikhail
Date Issued

2021-02-16

Publisher

Nature Research

Published in
Nature Communications
Volume

12

Issue

1

Article Number

1074

Subjects

Multidisciplinary Sciences

•

Science & Technology - Other Topics

•

cryo-em structure

•

nicotinic acetylcholine-receptor

•

gated ion channels

•

ligand-binding

•

conformational transitions

•

high-throughput

•

force-field

•

activation

•

reveal

•

states

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LBTC  
Available on Infoscience
April 24, 2021
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/177629
Logo EPFL, École polytechnique fédérale de Lausanne
  • Contact
  • infoscience@epfl.ch

  • Follow us on Facebook
  • Follow us on Instagram
  • Follow us on LinkedIn
  • Follow us on X
  • Follow us on Youtube
AccessibilityLegal noticePrivacy policyCookie settingsEnd User AgreementGet helpFeedback

Infoscience is a service managed and provided by the Library and IT Services of EPFL. © EPFL, tous droits réservés