8C20

Tetrameric 5-HT3aR in Salipro (holo state, symmetric)

Summary for 8C20

• Entry DOI: 10.2210/pdb8c20/pdb
• Related: 8C1Z
• EMDB information: 16386
• Descriptor: 5-hydroxytryptamine receptor 3A, SEROTONIN (2 entities in total)
• Functional Keywords: 5-ht3r, serotonin, receptor, tetramer, ion channel, membrane protein
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 4
• Total formula weight: 243024.77

Authors

Introini, B.,Kudryashev, M. (deposition date: 2022-12-21, release date: 2024-07-10, Last modification date: 2024-10-23)

Primary citation

Introini, B.,Cui, W.,Chu, X.,Zhang, Y.,Alves, A.C.,Eckhardt-Strelau, L.,Golusik, S.,Tol, M.,Vogel, H.,Yuan, S.,Kudryashev, M.
Structure of tetrameric forms of the serotonin-gated 5-HT3 A receptor ion channel.
Embo J., 43:4451-4471, 2024

PubMed Abstract: 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.

PubMed: 39232129
DOI: 10.1038/s44318-024-00191-5

Experimental method

ELECTRON MICROSCOPY (3.5 Å)