7YM8

Cryo-EM structure of Nb29-alpha1AAR-miniGsq complex bound to oxymetazoline

Summary for 7YM8

• Entry DOI: 10.2210/pdb7ym8/pdb
• EMDB information: 33924
• Descriptor: miniGsq, alpha1A adrenergic receptor, nanobody 29, ... (5 entities in total)
• Functional Keywords: gpcr, nanobody, agonist, complex, membrane protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 98870.89

Authors

Toyoda, Y.,Zhu, A.,Yan, C.,Kobilka, B.K.,Liu, X. (deposition date: 2022-07-27, release date: 2023-07-05, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (2.92 Å)