We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Structural basis of α<sub>1A</sub>-adrenergic receptor activation and recognition by an extracellular nanobody.
- Authors
Toyoda, Yosuke; Zhu, Angqi; Kong, Fang; Shan, Sisi; Zhao, Jiawei; Wang, Nan; Sun, Xiaoou; Zhang, Linqi; Yan, Chuangye; Kobilka, Brian K.; Liu, Xiangyu
- Abstract
The α1A-adrenergic receptor (α1AAR) belongs to the family of G protein-coupled receptors that respond to adrenaline and noradrenaline. α1AAR is involved in smooth muscle contraction and cognitive function. Here, we present three cryo-electron microscopy structures of human α1AAR 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 α1AAR 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 α1AAR 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. α1A-adrenergic receptor (α1AAR) regulates smooth muscle contraction and cognitive functions. Here, authors provide structural insight into α1AAR activation and binding modes of the orthosteric ligands and an extracellular allosteric nanobody.
- Subjects
SMOOTH muscle contraction; G protein coupled receptors; ADRENERGIC receptors; LIGAND binding (Biochemistry); NORADRENALINE; COGNITIVE ability; ADRENALINE
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-39310-x