Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Zhang, Y; Dijkman, PM; Zou, R; Zandl-Lang, M; Sanchez, RM; Eckhardt-Strelau, L; Köfeler, H; Vogel, H; Yuan, S; Kudryashev, M.
Asymmetric opening of the homopentameric 5-HT3A serotonin receptor in lipid bilayers.
Nat Commun. 2021; 12(1):1074-1074
Doi: 10.1038/s41467-021-21016-7
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- Co-Autor*innen der Med Uni Graz
- Köfeler Harald
- Zandl-Lang Martina
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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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Apoproteins - chemistry
- Apoproteins - metabolism
- Cell Line -
- Cryoelectron Microscopy -
- Lipid Bilayers - metabolism
- Lipids - chemistry
- Mice -
- Models, Biological -
- Models, Molecular -
- Protein Conformation -
- Protein Multimerization -
- Protein Subunits - chemistry
- Protein Subunits - metabolism
- Receptors, Serotonin, 5-HT3 - chemistry
- Receptors, Serotonin, 5-HT3 - metabolism
- Receptors, Serotonin, 5-HT3 - ultrastructure
- Serotonin - pharmacology