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-Structure paper
タイトル | Structural basis of α-adrenergic receptor activation and recognition by an extracellular nanobody. |
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ジャーナル・号・ページ | Nat Commun, Vol. 14, Issue 1, Page 3655, Year 2023 |
掲載日 | 2023年6月20日 |
著者 | Yosuke Toyoda / Angqi Zhu / Fang Kong / Sisi Shan / Jiawei Zhao / Nan Wang / Xiaoou Sun / Linqi Zhang / Chuangye Yan / Brian K Kobilka / Xiangyu Liu / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Commun / PubMed:37339967 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.92 - 3.52 Å |
構造データ | EMDB-33924, PDB-7ym8: EMDB-33928, PDB-7ymh: EMDB-33930, PDB-7ymj: |
化合物 | ChemComp-J5C: ChemComp-Y01: ChemComp-E5E: ChemComp-JGX: |
由来 |
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キーワード | MEMBRANE PROTEIN / GPCR / Nanobody / Agonist / Complex / Antagonist |