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TitleCryo-EM structures of the β adrenergic receptor bound to solabegron and isoproterenol.
Journal, issue, pagesBiochem Biophys Res Commun, Vol. 611, Page 158-164, Year 2022
Publish dateJun 30, 2022
AuthorsIkko Nureki / Kazuhiro Kobayashi / Tatsuki Tanaka / Kanae Demura / Asuka Inoue / Wataru Shihoya / Osamu Nureki /
PubMed AbstractThe 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- ...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.
External linksBiochem Biophys Res Commun / PubMed:35489202
MethodsEM (single particle)
Resolution3.9 Å
Structure data

33228

7xji

EMDB-33228, PDB-7xji:
Solabegron-activated dog beta3 adrenergic receptor
Method: EM (single particle) / Resolution: 3.9 Å

Chemicals

ChemComp-EI5:
3-[3-[2-[[(2~{S})-2-(3-chlorophenyl)-2-oxidanyl-ethyl]amino]ethylamino]phenyl]benzoic acid

Source
  • homo sapiens (human)
  • rattus norvegicus (Norway rat)
  • bos taurus (cattle)
  • unidentified (others)
  • canis lupus familiaris (dog)
KeywordsMEMBRANE PROTEIN / GPCR

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