8IRT

Dopamine Receptor D3R-Gi-Rotigotine complex

8IRT の概要

• エントリーDOI: 10.2210/pdb8irt/pdb
• EMDBエントリー: 35685
• 分子名称: Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ScFv16, ... (7 entities in total)
• 機能のキーワード: dopamine, dopamine receptor, gpcr, d3r, gi, rotigotine, polypharmacology parkinson's disease, restless legs syndrome, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 173789.45

構造登録者

Xu, P.,Huang, S.,Zhuang, Y.,Mao, C.,Zhang, Y.,Wang, Y.,Li, H.,Jiang, Y.,Zhang, Y.,Xu, H.E. (登録日: 2023-03-19, 公開日: 2023-06-07, 最終更新日: 2024-10-23)

主引用文献

Xu, P.,Huang, S.,Krumm, B.E.,Zhuang, Y.,Mao, C.,Zhang, Y.,Wang, Y.,Huang, X.P.,Liu, Y.F.,He, X.,Li, H.,Yin, W.,Jiang, Y.,Zhang, Y.,Roth, B.L.,Xu, H.E.
Structural genomics of the human dopamine receptor system.
Cell Res., 33:604-616, 2023

PubMed Abstract: The dopaminergic system, including five dopamine receptors (D1R to D5R), plays essential roles in the central nervous system (CNS); and ligands that activate dopamine receptors have been used to treat many neuropsychiatric disorders, including Parkinson's Disease (PD) and schizophrenia. Here, we report cryo-EM structures of all five subtypes of human dopamine receptors in complex with G protein and bound to the pan-agonist, rotigotine, which is used to treat PD and restless legs syndrome. The structures reveal the basis of rotigotine recognition in different dopamine receptors. Structural analysis together with functional assays illuminate determinants of ligand polypharmacology and selectivity. The structures also uncover the mechanisms of dopamine receptor activation, unique structural features among the five receptor subtypes, and the basis of G protein coupling specificity. Our work provides a comprehensive set of structural templates for the rational design of specific ligands to treat CNS diseases targeting the dopaminergic system.

PubMed: 37221270
DOI: 10.1038/s41422-023-00808-0

実験手法

ELECTRON MICROSCOPY (2.7 Å)