Structure of tetrameric forms of the serotonin-gated 5-HT3
Cryo-EM
Ion Channels
Pentameric Ligand-gated Ion Channels
Serotonin Receptors
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
04 Sep 2024
04 Sep 2024
Historique:
received:
19
03
2024
accepted:
15
07
2024
revised:
16
06
2024
medline:
5
9
2024
pubmed:
5
9
2024
entrez:
4
9
2024
Statut:
aheadofprint
Résumé
Multimeric membrane proteins are produced in the endoplasmic reticulum and transported to their target membranes which, for ion channels, is typically the plasma membrane. Despite the availability of many fully assembled channel structures, our understanding of assembly intermediates, multimer assembly mechanisms, and potential functions of non-standard assemblies is limited. We demonstrate that the pentameric ligand-gated serotonin 5-HT3A receptor (5-HT3AR) can assemble to tetrameric forms and report the structures of the tetramers in plasma membranes of cell-derived microvesicles and in membrane memetics using cryo-electron microscopy and tomography. The tetrameric structures have near-symmetric transmembrane domains, and asymmetric extracellular domains, and can bind serotonin molecules. Computer simulations, based on our cryo-EM structures, were used to decipher the assembly pathway of pentameric 5-HT3R and suggest a potential functional role for the tetrameric receptors.
Identifiants
pubmed: 39232129
doi: 10.1038/s44318-024-00191-5
pii: 10.1038/s44318-024-00191-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Forschungsgemeinschaft (DFG)
ID : KU3222/2-1,KU3222/3-1
Organisme : CAS | Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences (SIAT, CAS)
ID : JCYJ20200109114818703
Organisme : Guangdong province
ID : 2019QN01Y306
Organisme : Guangdong province
ID : Academician Work funding
Organisme : Shenzhen Key Laboratory for Computer Aided Drug Discovery in SIAT
ID : ZDSYS20201230165400001
Organisme : The Chinese Academy of Science President's International Fellowship Initiative
ID : 2020FSB0003
Organisme : NSFC-SNF
ID : 32161133022
Organisme : Shenzhen Government ( )
ID : Top-Talent Working Funding
Organisme : Guangdong Province
ID : Academician Work funding
Informations de copyright
© 2024. The Author(s).
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