登録情報 データベース : EMDB  /  ID : EMD-30410タイトル Dopamine Receptor D3R-Gi-Pramipexole complex   複合体 : Dopamine Receptor D3R-Gi-Pramipexole complex複合体 : Guanine nucleotide-binding proteinタンパク質・ペプチド : Guanine nucleotide-binding protein G(i) subunit alpha-1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複合体 : scfv16複合体 : chimera protein of Soluble cytochrome b562 and D(3) dopamine receptorタンパク質・ペプチド : Soluble cytochrome b562,D(3) dopamine receptorリガンド : (6S)-N6-propyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine /   /  機能・相同性 分子機能 ドメイン・相同性 構成要素 
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 ジャーナル : Mol Cell  /  年 : 2021タイトル : Structures of the human dopamine D3 receptor-G complexes.著者: Peiyu Xu / Sijie Huang / Chunyou Mao / Brian E Krumm / X Edward Zhou / Yangxia Tan / Xi-Ping Huang / Yongfeng Liu / Dan-Dan Shen / Yi Jiang / Xuekui Yu / Hualiang Jiang / Karsten Melcher /  ... 著者 : Peiyu Xu  /  Sijie Huang  /  Chunyou Mao  /  Brian E Krumm  /  X Edward Zhou  /  Yangxia Tan  /  Xi-Ping Huang  /  Yongfeng Liu  /  Dan-Dan Shen  /  Yi Jiang  /  Xuekui Yu  /  Hualiang Jiang  /  Karsten Melcher  /  Bryan L Roth  /  Xi Cheng  /  Yan Zhang  /  H Eric Xu  /  要旨 : The dopamine system, including five dopamine receptors (D1R-D5R), plays essential roles in the central nervous system (CNS), and ligands that activate dopamine receptors have been used to treat many  ... The dopamine system, including five dopamine receptors (D1R-D5R), plays essential roles in the central nervous system (CNS), and ligands that activate dopamine receptors have been used to treat many neuropsychiatric disorders. Here, we report two cryo-EM structures of human D3R in complex with an inhibitory G protein and bound to the D3R-selective agonists PD128907 and pramipexole, the latter of which is used to treat patients with Parkinson's disease. The structures reveal agonist binding modes distinct from the antagonist-bound D3R structure and conformational signatures for ligand-induced receptor activation. Mutagenesis and homology modeling illuminate determinants of ligand specificity across dopamine receptors and the mechanisms for G protein coupling. Collectively our work reveals the basis of agonist binding and ligand-induced receptor activation and provides structural templates for designing specific ligands to treat CNS diseases targeting the dopaminergic system. 履歴 登録 2020年7月29日 - ヘッダ(付随情報) 公開 2021年3月10日 - マップ公開 2021年3月10日 - 更新 2024年10月23日 - 現状 2024年10月23日 処理サイト : PDBj /  状態 : 公開
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