6K42

cryo-EM structure of alpha2BAR-Gi1 complex

6K42 の概要

• エントリーDOI: 10.2210/pdb6k42/pdb
• EMDBエントリー: 9911 9912
• 分子名称: 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)
• 機能のキーワード: gpcr, complex, cryo-em, membrane protein
• 由来する生物種: Bos taurus (Bovine); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 178062.44

構造登録者

Yuan, D.,Liu, Z.,Wang, H.W.,Kobilka, B.K. (登録日: 2019-05-23, 公開日: 2020-04-15, 最終更新日: 2024-10-30)

主引用文献

Yuan, D.,Liu, Z.,Kaindl, J.,Maeda, S.,Zhao, J.,Sun, X.,Xu, J.,Gmeiner, P.,Wang, H.W.,Kobilka, B.K.
Activation of the alpha2Badrenoceptor by the sedative sympatholytic dexmedetomidine.
Nat.Chem.Biol., 16:507-512, 2020

PubMed Abstract: The α adrenergic receptors (αARs) are G protein-coupled receptors (GPCRs) that respond to adrenaline and noradrenaline and couple to the Gi/o family of G proteins. αARs play important roles in regulating the sympathetic nervous system. Dexmedetomidine is a highly selective αAR agonist used in post-operative patients as an anxiety-reducing, sedative medicine that decreases the requirement for opioids. As is typical for selective αAR agonists, dexmedetomidine consists of an imidazole ring and a substituted benzene moiety lacking polar groups, which is in contrast to βAR-selective agonists, which share an ethanolamine group and an aromatic system with polar, hydrogen-bonding substituents. To better understand the structural basis for the selectivity and efficacy of adrenergic agonists, we determined the structure of the αAR in complex with dexmedetomidine and Go at a resolution of 2.9 Å by single-particle cryo-EM. The structure reveals the mechanism of αAR-selective activation and provides insights into Gi/o coupling specificity.

PubMed: 32152538
DOI: 10.1038/s41589-020-0492-2

実験手法

ELECTRON MICROSCOPY (4.1 Å)