6Y59

5-HT3A receptor in Salipro (apo, C5 symmetric)

Summary for 6Y59

• Entry DOI: 10.2210/pdb6y59/pdb
• Related: 6Y5A 6Y5B
• EMDB information: 10691 10692 10693
• Descriptor: 5-hydroxytryptamine receptor 3A (1 entity in total)
• Functional Keywords: pentameric ligand-gated ion channel, plgic, serotonin 5-ht3a receptor, 5-ht3ar, salipro, membrane protein
• Biological source: Mus musculus (House mouse)
• Total number of polymer chains: 5
• Total formula weight: 303340.43

Authors

Zhang, Y.,Dijkman, P.M.,Zou, R.,Zandl-Lang, M.,Sanchez, R.M.,Eckhardt-Strelau, L.,Koefeler, H.,Vogel, H.,Yuan, S.,Kudryashev, M. (deposition date: 2020-02-25, release date: 2020-12-23, Last modification date: 2024-10-23)

Primary citation

Zhang, Y.,Dijkman, P.M.,Zou, R.,Zandl-Lang, M.,Sanchez, R.M.,Eckhardt-Strelau, L.,Kofeler, H.,Vogel, H.,Yuan, S.,Kudryashev, M.
Asymmetric opening of the homopentameric 5-HT 3A serotonin receptor in lipid bilayers.
Nat Commun, 12:1074-1074, 2021

PubMed 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 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.

PubMed: 33594077
DOI: 10.1038/s41467-021-21016-7

Experimental method

ELECTRON MICROSCOPY (3.2 Å)