- EMDB-32964: Cryo-EM structure of the fenoldopam-bound D1 dopamine receptor an... -
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データベース: EMDB / ID: EMD-32964
タイトル
Cryo-EM structure of the fenoldopam-bound D1 dopamine receptor and mini-Gs complex
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複合体: Cryo-EM structure of the fenoldopam-bound D1R-miniGs complex
複合体: the fenoldopam-bound D1R-miniGs
複合体: Gbeta-1gama-2
タンパク質・ペプチド: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
タンパク質・ペプチド: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
タンパク質・ペプチド: D(1A) dopamine receptor
タンパク質・ペプチド: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
ジャーナル: Nat Commun / 年: 2022 タイトル: Ligand recognition and biased agonism of the D1 dopamine receptor. 著者: Xiao Teng / Sijia Chen / Yingying Nie / Peng Xiao / Xiao Yu / Zhenhua Shao / Sanduo Zheng / 要旨: Dopamine receptors are widely distributed in the central nervous system and are important therapeutic targets for treatment of various psychiatric and neurological diseases. Here, we report three ...Dopamine receptors are widely distributed in the central nervous system and are important therapeutic targets for treatment of various psychiatric and neurological diseases. Here, we report three cryo-electron microscopy structures of the D1 dopamine receptor (D1R)-Gs complex bound to two agonists, fenoldopam and tavapadon, and a positive allosteric modulator LY3154207. The structure reveals unusual binding of two fenoldopam molecules, one to the orthosteric binding pocket (OBP) and the other to the extended binding pocket (EBP). In contrast, one elongated tavapadon molecule binds to D1R, extending from OBP to EBP. Moreover, LY3154207 stabilizes the second intracellular loop of D1R in an alpha helical conformation to efficiently engage the G protein. Through a combination of biochemical, biophysical and cellular assays, we further show that the broad conformation stabilized by two fenoldopam molecules and interaction between TM5 and the agonist are important for biased signaling of D1R.
全体 : Cryo-EM structure of the fenoldopam-bound D1R-miniGs complex
全体
名称: Cryo-EM structure of the fenoldopam-bound D1R-miniGs complex
要素
複合体: Cryo-EM structure of the fenoldopam-bound D1R-miniGs complex
複合体: the fenoldopam-bound D1R-miniGs
複合体: Gbeta-1gama-2
タンパク質・ペプチド: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
タンパク質・ペプチド: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
タンパク質・ペプチド: D(1A) dopamine receptor
タンパク質・ペプチド: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short