9AS8

Global reconstruction of 5-HT2AR bound to psilocin in complex with a mini-Gq protein and scFv16 obtained by cryo-electron microscopy (cryoEM)

9AS8 の概要

• エントリーDOI: 10.2210/pdb9as8/pdb
• EMDBエントリー: 43808
• 分子名称: 5-hydroxytryptamine receptor 2A, G subunit q (Gi2-mini-Gq chimeric), Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (6 entities in total)
• 機能のキーワード: gpcr, g-protein coupled receptor, 5-ht2ar, serotonin, psychedelics, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 156886.20

構造登録者

Gumpper, R.H.,Fay, J.F.,Roth, B.L. (登録日: 2024-02-24, 公開日: 2025-04-02, 最終更新日: 2025-05-21)

主引用文献

Gumpper, R.H.,Jain, M.K.,Kim, K.,Sun, R.,Sun, N.,Xu, Z.,DiBerto, J.F.,Krumm, B.E.,Kapolka, N.J.,Kaniskan, H.U.,Nichols, D.E.,Jin, J.,Fay, J.F.,Roth, B.L.
The structural diversity of psychedelic drug actions revealed.
Nat Commun, 16:2734-2734, 2025

PubMed Abstract: There is currently a resurgence in exploring the utility of classical psychedelics to treat depression, addiction, anxiety disorders, cluster headaches, and many other neuropsychiatric disorders. A biological target of these compounds, and a hypothesized target for their therapeutic actions, is the 5-HT serotonin receptor. Here, we present 7 cryo-EM structures covering all major compound classes of psychedelic and non-psychedelic agonists, including a β-arrestin-biased compound RS130-180. Identifying the molecular interactions between various psychedelics and the 5-HT receptor reveals both common and distinct motifs among the examined psychedelic chemotypes. These findings lead to a broader mechanistic understanding of 5-HT activation, which can catalyze the development of novel chemotypes with potential therapeutic utility and fewer side effects.

PubMed: 40108183
DOI: 10.1038/s41467-025-57956-7

実験手法

ELECTRON MICROSCOPY (2.54 Å)