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| Item Type: | Article |
|---|---|
| Title: | Asymmetric opening of the homopentameric 5-HT(3A) serotonin receptor in lipid bilayers |
| Creators Name: | Zhang, Y. and Dijkman, P.M. and Zou, R. and Zandl-Lang, M. and Sanchez, R.M. and Eckhardt-Strelau, L. and Köfeler, H. and Vogel, H. and Yuan, S. and Kudryashev, M. |
| 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-HT(3A) 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. |
| Keywords: | 5-HT3 Serotonin Receptors, Apoproteins, Biological Models, Cell Line, Cryoelectron Microscopy, Lipid Bilayers, Lipids, Molecular Models, Protein Conformation, Protein Multimerization, Protein Subunits, Serotonin, Animals, Mice |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 12 |
| Number: | 1 |
| Page Range: | 1074 |
| Date: | 16 February 2021 |
| Official Publication: | https://doi.org/10.1038/s41467-021-21016-7 |
| PubMed: | View item in PubMed |
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