7JVR

Cryo-EM structure of Bromocriptine-bound dopamine receptor 2 in complex with Gi protein

7JVR の概要

• エントリーDOI: 10.2210/pdb7jvr/pdb
• EMDBエントリー: 22511
• 分子名称: Soluble cytochrome b562,D(2) dopamine receptor, Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (6 entities in total)
• 機能のキーワード: dopamine receptor 2, gi protein, bromocriptine, signaling protein
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 183124.12

構造登録者

Zhuang, Y.,Xu, P.,Mao, C.,Wang, L.,Krumm, B.,Zhou, X.E.,Huang, S.,Liu, H.,Cheng, X.,Huang, X.-P.,Sheng, D.-D.,Xu, T.,Liu, Y.-F.,Wang, Y.,Guo, J.,Jiang, Y.,Jiang, H.,Melcher, K.,Roth, B.L.,Zhang, Y.,Zhang, C.,Xu, H.E. (登録日: 2020-08-22, 公開日: 2021-02-24, 最終更新日: 2025-05-28)

主引用文献

Zhuang, Y.,Xu, P.,Mao, C.,Wang, L.,Krumm, B.,Zhou, X.E.,Huang, S.,Liu, H.,Cheng, X.,Huang, X.P.,Shen, D.D.,Xu, T.,Liu, Y.F.,Wang, Y.,Guo, J.,Jiang, Y.,Jiang, H.,Melcher, K.,Roth, B.L.,Zhang, Y.,Zhang, C.,Xu, H.E.
Structural insights into the human D1 and D2 dopamine receptor signaling complexes.
Cell, 184:931-942.e18, 2021

PubMed Abstract: The D1- and D2-dopamine receptors (D1R and D2R), which signal through G and G, respectively, represent the principal stimulatory and inhibitory dopamine receptors in the central nervous system. D1R and D2R also represent the main therapeutic targets for Parkinson's disease, schizophrenia, and many other neuropsychiatric disorders, and insight into their signaling is essential for understanding both therapeutic and side effects of dopaminergic drugs. Here, we report four cryoelectron microscopy (cryo-EM) structures of D1R-G and D2R-G signaling complexes with selective and non-selective dopamine agonists, including two currently used anti-Parkinson's disease drugs, apomorphine and bromocriptine. These structures, together with mutagenesis studies, reveal the conserved binding mode of dopamine agonists, the unique pocket topology underlying ligand selectivity, the conformational changes in receptor activation, and potential structural determinants for G protein-coupling selectivity. These results provide both a molecular understanding of dopamine signaling and multiple structural templates for drug design targeting the dopaminergic system.

PubMed: 33571431
DOI: 10.1016/j.cell.2021.01.027

実験手法

ELECTRON MICROSCOPY (2.8 Å)