7YMJ

Cryo-EM structure of alpha1AAR-Nb6 complex bound to tamsulosin

7YMJ の概要

• エントリーDOI: 10.2210/pdb7ymj/pdb
• 関連するPDBエントリー: 7YM8 7YMH
• EMDBエントリー: 33924 33928 33930
• 分子名称: alpha1A-adrenergic receptor, Nb6, Tamsulosin (3 entities in total)
• 機能のキーワード: gpcr, nanobody, antagonist, complex, membrane protein
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 57728.28

構造登録者

Toyoda, Y.,Zhu, A.,Yan, C.,Kobilka, B.K.,Liu, X. (登録日: 2022-07-28, 公開日: 2023-07-05, 最終更新日: 2025-07-02)

主引用文献

Toyoda, Y.,Zhu, A.,Kong, F.,Shan, S.,Zhao, J.,Wang, N.,Sun, X.,Zhang, L.,Yan, C.,Kobilka, B.K.,Liu, X.
Structural basis of alpha 1A -adrenergic receptor activation and recognition by an extracellular nanobody.
Nat Commun, 14:3655-3655, 2023

PubMed Abstract: The αadrenergic receptor (αAR) belongs to the family of G protein-coupled receptors that respond to adrenaline and noradrenaline. αAR is involved in smooth muscle contraction and cognitive function. Here, we present three cryo-electron microscopy structures of human αAR bound to the endogenous agonist noradrenaline, its selective agonist oxymetazoline, and the antagonist tamsulosin, with resolutions range from 2.9 Å to 3.5 Å. Our active and inactive αAR structures reveal the activation mechanism and distinct ligand binding modes for noradrenaline compared with other adrenergic receptor subtypes. In addition, we identified a nanobody that preferentially binds to the extracellular vestibule of αAR when bound to the selective agonist oxymetazoline. These results should facilitate the design of more selective therapeutic drugs targeting both orthosteric and allosteric sites in this receptor family.

PubMed: 37339967
DOI: 10.1038/s41467-023-39310-x

実験手法

ELECTRON MICROSCOPY (3.35 Å)