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-Structure paper
タイトル | Cryo-EM structures of the β adrenergic receptor bound to solabegron and isoproterenol. |
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ジャーナル・号・ページ | Biochem Biophys Res Commun, Vol. 611, Page 158-164, Year 2022 |
掲載日 | 2022年6月30日 |
![]() | Ikko Nureki / Kazuhiro Kobayashi / Tatsuki Tanaka / Kanae Demura / Asuka Inoue / Wataru Shihoya / Osamu Nureki / ![]() |
PubMed 要旨 | 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- ...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. |
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手法 | EM (単粒子) |
解像度 | 3.9 Å |
構造データ | EMDB-33228, PDB-7xji: |
化合物 | ![]() ChemComp-EI5: |
由来 |
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![]() | MEMBRANE PROTEIN / GPCR |