7X5H

Serotonin 5A (5-HT5A) receptor-Gi protein complex

Summary for 7X5H

• Entry DOI: 10.2210/pdb7x5h/pdb
• EMDB information: 33014
• Descriptor: Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (6 entities in total)
• Functional Keywords: serotonin, 5-ht, gpcr, gi, 5-ct, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 196253.74

Authors

Tan, Y.,Xu, P.,Huang, S.,Xu, H.E.,Jiang, Y. (deposition date: 2022-03-04, release date: 2022-09-14, Last modification date: 2022-09-21)

Primary citation

Tan, Y.,Xu, P.,Huang, S.,Yang, G.,Zhou, F.,He, X.,Ma, H.,Xu, H.E.,Jiang, Y.
Structural insights into the ligand binding and G i coupling of serotonin receptor 5-HT 5A .
Cell Discov, 8:50-50, 2022

PubMed Abstract: 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.

PubMed: 35610220
DOI: 10.1038/s41421-022-00412-3

Experimental method

ELECTRON MICROSCOPY (3.1 Å)