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TitleAsymmetric opening of the homopentameric 5-HT serotonin receptor in lipid bilayers.
Journal, issue, pagesNat Commun, Vol. 12, Issue 1, Page 1074, Year 2021
Publish dateFeb 16, 2021
AuthorsYingyi Zhang / Patricia M Dijkman / Rongfeng Zou / Martina Zandl-Lang / Ricardo M Sanchez / Luise Eckhardt-Strelau / Harald Köfeler / Horst Vogel / Shuguang Yuan / Mikhail Kudryashev /
PubMed AbstractPentameric 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.
External linksNat Commun / PubMed:33594077 / PubMed Central
MethodsEM (single particle)
Resolution2.8 - 3.2 Å
Structure data

10691

6y59

EMDB-10691, PDB-6y59:
5-HT3A receptor in Salipro (apo, C5 symmetric)
Method: EM (single particle) / Resolution: 3.2 Å

10692

6y5a

EMDB-10692, PDB-6y5a:
Serotonin-bound 5-HT3A receptor in Salipro
Method: EM (single particle) / Resolution: 2.8 Å

10693

6y5b

EMDB-10693, PDB-6y5b:
5-HT3A receptor in Salipro (apo, asymmetric)
Method: EM (single particle) / Resolution: 3.1 Å

Chemicals

ChemComp-SRO:
SEROTONIN / neurotransmitter*YM / Serotonin

Source
  • mus musculus (house mouse)
KeywordsMEMBRANE PROTEIN / Pentameric ligand-gated ion channel / pLGIC / serotonin 5-HT3A receptor / 5-HT3AR / Salipro / serotonin / agonist-bound / asymmetric

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