7EJK

Structure of the alpha2A-adrenergic receptor GoA signaling complex bound to oxymetazoline

7EJK の概要

• エントリーDOI: 10.2210/pdb7ejk/pdb
• 関連するPDBエントリー: 7EJ8 7EJA 7EL0
• EMDBエントリー: 31162
• 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, ... (6 entities in total)
• 機能のキーワード: alpha2a-adrenergic receptor, signaling complex, cryo-em, 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: 170228.23

構造登録者

Xu, J.,Cao, S.,Liu, Z.,Du, Y. (登録日: 2021-04-02, 公開日: 2022-04-13, 最終更新日: 2024-10-23)

主引用文献

Xu, J.,Cao, S.,Hubner, H.,Weikert, D.,Chen, G.,Lu, Q.,Yuan, D.,Gmeiner, P.,Liu, Z.,Du, Y.
Structural insights into ligand recognition, activation, and signaling of the alpha 2A adrenergic receptor.
Sci Adv, 8:eabj5347-eabj5347, 2022

PubMed Abstract: The α adrenergic receptor (αAR) is a G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor that mediates important physiological functions in response to the endogenous neurotransmitters norepinephrine and epinephrine, as well as numerous chemically distinct drugs. However, the molecular mechanisms of drug actions remain poorly understood. Here, we report the cryo-electron microscopy structures of the human αAR-GoA complex bound to norepinephrine and three imidazoline derivatives (brimonidine, dexmedetomidine, and oxymetazoline). Together with mutagenesis and functional data, these structures provide important insights into the molecular basis of ligand recognition, activation, and signaling at the αAR. Further structural analyses uncover different molecular determinants between αAR and βARs for recognition of norepinephrine and key regions that determine the G protein coupling selectivity. Overall, our studies provide a framework for understanding the signal transduction of the adrenergic system at the atomic level, which will facilitate rational structure-based discovery of safer and more effective medications for αAR.

PubMed: 35245122
DOI: 10.1126/sciadv.abj5347

実験手法

ELECTRON MICROSCOPY (3.4 Å)