Structures of the human dopamine D3 receptor-G(i) complexes

doi:10.1016/j.molcel.2021.01.003

	Structures of the human dopamine D3 receptor-G(i) complexes
	Xu, Peiyu 1,2,3,4; Huang, Sijie3,4,5 ; Mao, Chunyou 1,2; Krumm, Brian E.6; Zhou, X. Edward 7; Tan, Yangxia3,4,5 ; Huang, Xi-Ping 6; Liu, Yongfeng 6; Shen, Dan-Dan 1,2; Jiang, Yi 3; Yu, Xuekui 3,8; Jiang, Hualiang 3,9; Melcher, Karsten 7; Roth, Bryan L.6; Cheng, Xi 3,9; Zhang, Yan 1,2,10,11,12; Xu, H. Eric3,4,5
	2021
发表期刊	MOLECULAR CELL (IF:14.5[JCR-2023],16.6[5-Year])
ISSN	1097-2765
EISSN	1097-4164
卷号	81 期号:6 页码:1147+
发表状态	已发表
DOI	10.1016/j.molcel.2021.01.003
摘要	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(i) 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.
收录类别	SCIE
语种	英语
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
WOS类目	Biochemistry & Molecular Biology ; Cell Biology
WOS记录号	WOS:000632670800006
出版者	CELL PRESS
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/126225
专题	生命科学与技术学院_博士生生命科学与技术学院_特聘教授组_徐华强组生命科学与技术学院_硕士生
通讯作者	Roth, Bryan L.; Cheng, Xi; Zhang, Yan; Xu, H. Eric
作者单位	1.Zhejiang Univ, Dept Biophys, Sir Run Run Shaw Hosp, Sch Med, Hangzhou 310058, Peoples R China; 2.Zhejiang Univ, Dept Pathol, Sir Run Run Shaw Hosp, Sch Med, Hangzhou 310058, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China; 6.Univ N Carolina, Dept Pharmacol, Sch Med, Chapel Hill, NC 27514 USA; 7.Van Andel Inst, Ctr Canc & Cell Biol, Program Struct Biol, Grand Rapids, MI 49503 USA; 8.Chinese Acad Sci, Cryoelectron Microscopy Res Ctr, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 9.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 10.Zhejiang Univ, Zhejiang Lab Syst & Precison Med, Med Ctr, Hangzhou 311121, Peoples R China; 11.Zhejiang Univ, MOE Frontier Sci Ctr Brain Res & Brain Machine In, Sch Med, Hangzhou 310058, Zhejiang, Peoples R China; 12.Key Lab Immun & Inflammatory Dis Zhejiang Prov, Hangzhou 310058, Zhejiang, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Xu, Peiyu,Huang, Sijie,Mao, Chunyou,et al. Structures of the human dopamine D3 receptor-G(i) complexes[J]. MOLECULAR CELL,2021,81(6):1147+.
APA	Xu, Peiyu.,Huang, Sijie.,Mao, Chunyou.,Krumm, Brian E..,Zhou, X. Edward.,...&Xu, H. Eric.(2021).Structures of the human dopamine D3 receptor-G(i) complexes.MOLECULAR CELL,81(6),1147+.
MLA	Xu, Peiyu,et al."Structures of the human dopamine D3 receptor-G(i) complexes".MOLECULAR CELL 81.6(2021):1147+.