9DYE

Buspirone-bound serotonin 1A (5-HT1A) receptor-Goa protein complex

9DYE の概要

• エントリーDOI: 10.2210/pdb9dye/pdb
• EMDBエントリー: 47301
• 分子名称: Guanine nucleotide-binding protein G(o) subunit alpha, 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, ... (7 entities in total)
• 機能のキーワード: gpcr signaling complex, serotonin receptor, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 151414.99

構造登録者

Warren, A.L.,Zilberg, G.,Wacker, D. (登録日: 2024-10-14, 公開日: 2025-08-13)

主引用文献

Warren, A.L.,Zilberg, G.,Abbassi, A.,Abraham, A.,Yang, S.,Wacker, D.
Structural determinants of G protein subtype selectivity at the serotonin receptor 5-HT1A.
Sci Adv, 11:eadu9851-eadu9851, 2025

PubMed Abstract: Activation of the serotonin receptor 5-HT1A has been shown to regulate mood and cognition, making 5-HT1A an important target in the treatment of anxiety, depression, and psychosis. Although the receptor signals through inhibitory G proteins, more work is necessary to understand differences in transducer coupling and its relation to functional activity. To develop a molecular understanding of the differences underlying transducer coupling and activation, we performed structure-activity relationship studies of 5-HT1A with distinct G proteins. Through a combination of in vitro assays, we identified a potent partial agonist that selectively engages a G protein subtype. We further investigated the differences in G protein engagement at 5-HT1A with cryo-electron microscopy, determining structures of 5-HT1A bound to distinct ligands and G protein subtypes. Combined with subsequent structure-guided mutagenesis and signaling assays, our studies uncover both orthosteric and allosteric determinants of agonist-specific stimulation of distinct transducers.

PubMed: 40749070
DOI: 10.1126/sciadv.adu9851

実験手法

ELECTRON MICROSCOPY (2.9 Å)