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TitleStructure of tetrameric forms of the serotonin-gated 5-HT3 receptor ion channel.
Journal, issue, pagesEMBO J, Vol. 43, Issue 20, Page 4451-4471, Year 2024
Publish dateSep 4, 2024
AuthorsBianca Introini / Wenqiang Cui / Xiaofeng Chu / Yingyi Zhang / Ana Catarina Alves / Luise Eckhardt-Strelau / Sabrina Golusik / Menno Tol / Horst Vogel / Shuguang Yuan / Mikhail Kudryashev /
PubMed AbstractMultimeric 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 ...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.
External linksEMBO J / PubMed:39232129 / PubMed Central
MethodsEM (single particle) / EM (subtomogram averaging)
Resolution3.5 - 25.2 Å
Structure data

16384

8c1w

EMDB-16384, PDB-8c1w:
Tetrameric 5-HT3A receptor in Salipro (apo, asymmetric)
Method: EM (single particle) / Resolution: 3.9 Å

16385

8c1z

EMDB-16385, PDB-8c1z:
Tetrameric 5-HT3aR in Salipro (apo state, symmetric)
Method: EM (single particle) / Resolution: 3.8 Å

16386

8c20

EMDB-16386, PDB-8c20:
Tetrameric 5-HT3aR in Salipro (holo state, symmetric)
Method: EM (single particle) / Resolution: 3.5 Å

16387

8c21

EMDB-16387, PDB-8c21:
Tetrameric 5-HT3A receptor in Salipro (holo, asymmetric)
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-19419: sub-tomogram averaging results of tetrameric 5-HT3A receptor on cell-derived vesicles
Method: EM (subtomogram averaging) / Resolution: 25.2 Å

EMDB-19420: Sub-tomogram averaging results of pentameric 5-HT3A receptor on cell-derived vesicles
Method: EM (subtomogram averaging) / Resolution: 19.6 Å

Chemicals

ChemComp-SRO:
SEROTONIN / neurotransmitter*YM

Source
  • mus musculus (house mouse)
KeywordsMEMBRANE PROTEIN / 5-HT3R / Serotonin / receptor / tetramer / ion channel / ion channel MEMBRANE PROTEIN

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