Journal: Nat Commun / Year: 2021 Title: Asymmetric opening of the homopentameric 5-HT serotonin receptor in lipid bilayers. Authors: Yingyi Zhang / Patricia M Dijkman / Rongfeng Zou / Martina Zandl-Lang / Ricardo M Sanchez / Luise Eckhardt-Strelau / Harald Köfeler / Horst Vogel / Shuguang Yuan / Mikhail Kudryashev / 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 ...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-HT serotonin receptor (5HTR) 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 5HTR 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 5HTR by the membrane environment, and a model for asymmetric activation of the receptor.
History
Deposition
Feb 25, 2020
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Header (metadata) release
Dec 23, 2020
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Map release
Dec 23, 2020
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Update
Mar 3, 2021
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Current status
Mar 3, 2021
Processing site: PDBe / Status: Released
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EMPIAR-10381 (Title: Lipid-stabilised asymmetric open state of the 5-HT3A serotonin receptor Data size: 15.6 TB Data #1: Lipid-stabilised 5-HT3A serotonin receptor in asymmetric open state [micrographs - multiframe] Data #2: Lipid-stabilised 5-HT3A serotonin receptor in apo state forms (symmetric C5 apo and asymmetric C1 apo) [micrographs - multiframe])
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