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TitleStructural insights into the ligand binding and G coupling of serotonin receptor 5-HT.
Journal, issue, pagesCell Discov, Vol. 8, Issue 1, Page 50, Year 2022
Publish dateMay 24, 2022
AuthorsYangxia Tan / Peiyu Xu / Sijie Huang / Gong Yang / Fulai Zhou / Xinheng He / Honglei Ma / H Eric Xu / Yi Jiang /
PubMed Abstract5-hydroxytryptamine receptor 5A (5-HT) belongs to the 5-HT receptor family and signals through the G protein. It is involved in nervous system regulation and an attractive target for the treatment of ...5-hydroxytryptamine receptor 5A (5-HT) belongs to the 5-HT receptor family and signals through the G protein. It is involved in nervous system regulation and an attractive target for the treatment of psychosis, depression, schizophrenia, and neuropathic pain. 5-HT is the only G-coupled 5-HT receptor subtype lacking a high-resolution structure, which hampers the mechanistic understanding of ligand binding and G coupling for 5-HT. Here we report a cryo-electron microscopy structure of the 5-HT-G complex bound to 5-Carboxamidotryptamine (5-CT). Combined with functional analysis, this structure reveals the 5-CT recognition mechanism and identifies the receptor residue at 6.55 as a determinant of the 5-CT selectivity for G-coupled 5-HT receptors. In addition, 5-HT shows an overall conserved G protein coupling mode compared with other G-coupled 5-HT receptors. These findings provide comprehensive insights into the ligand binding and G protein coupling of G-coupled 5-HT receptors and offer a template for the design of 5-HT-selective drugs.
External linksCell Discov / PubMed:35610220 / PubMed Central
MethodsEM (single particle)
Resolution3.1 Å
Structure data

33014

7x5h

EMDB-33014, PDB-7x5h:
Serotonin 5A (5-HT5A) receptor-Gi protein complex
Method: EM (single particle) / Resolution: 3.1 Å

Chemicals

ChemComp-8K3:
3-(2-azanylethyl)-1H-indole-5-carboxamide / neurotransmitter, agonist*YM

Source
  • homo sapiens (human)
  • mus musculus (house mouse)
  • escherichia coli (E. coli)
KeywordsMEMBRANE PROTEIN / Serotonin / 5-HT / GPCR / Gi / 5-CT

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