7XJI

Solabegron-activated dog beta3 adrenergic receptor

Summary for 7XJI

• Entry DOI: 10.2210/pdb7xji/pdb
• EMDB information: 33228
• Descriptor: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Nanobody-35, ... (6 entities in total)
• Functional Keywords: gpcr, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 148415.63

Authors

Shihoya, W.,Nureki, O. (deposition date: 2022-04-18, release date: 2022-05-04, Last modification date: 2025-07-02)

Primary citation

Nureki, I.,Kobayashi, K.,Tanaka, T.,Demura, K.,Inoue, A.,Shihoya, W.,Nureki, O.
Cryo-EM structures of the beta 3 adrenergic receptor bound to solabegron and isoproterenol.
Biochem.Biophys.Res.Commun., 611:158-164, 2022

PubMed Abstract: The β-adrenergic receptor (βAR) is the most essential drug target for overactive bladder and has therapeutic potentials for the treatments of type 2 diabetes and obesity. Here, we report the cryo-electron microscopy structures of the βAR-G signaling complexes with the selective agonist, solabegron and the nonselective agonist, isoproterenol. Comparison of the isoproterenol-, mirabegron-, and solabegron-bound βAR structures revealed that the extracellular loop 2 changes its conformation depending on the bound agonist and plays an essential role in solabegron binding. Moreover, βAR has an intrinsically narrow exosite, regardless of the agonist type. This structural feature clearly explains why βAR prefers mirabegron and solabegron, as the narrow exosite is suitable for binding with agonists with elongated shapes. Our study deepens the understanding of the binding characteristics of βAR agonists and may pave the way for developing βAR-selective drugs.

PubMed: 35489202
DOI: 10.1016/j.bbrc.2022.04.065

Experimental method

ELECTRON MICROSCOPY (3.9 Å)