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

文献类型：期刊论文

作者Xu, Peiyu1,2,3,4; Huang, Sijie3,4,5; Mao, Chunyou1,2; Krumm, Brian E.6; Zhou, X. Edward7; Tan, Yangxia3,4,5; Huang, Xi-Ping6; Liu, Yongfeng6; Shen, Dan-Dan1,2; Jiang, Yi3
刊名MOLECULAR CELL
出版日期2021-03-18
卷号81期号:6页码:1147-+
ISSN号1097-2765
DOI10.1016/j.molcel.2021.01.003
通讯作者Roth, Bryan L.(bryan_roth@med.unc.edu) ; Cheng, Xi(xicheng@simm.ac.cn) ; Zhang, Yan(zhang_yan@zju.edu.cn) ; Xu, H. Eric(eric.xu@simm.ac.cn)
英文摘要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.
资助项目National Key R&D Programs of China[2018YFA0507002] ; Shanghai Municipal Science and Technology Major Project[2019SHZDZX02] ; CAS Strategic Priority Research Program[XDB37030103] ; National Key Basic Research Program of China[2019YFA0508800] ; National Natural Science Foundation of China[81922071] ; Zhejiang Province Natural Science Fund for Excellent Young Scholars[LR19H310001] ; Fundamental Research Funds for the Central Universities[2019XZZX001-01-06] ; Fund of Youth Innovation Promotion Association[2018319 Y8G7011009] ; Science and Technology Commission of Shanghai Municipal[20431900100] ; Jack Ma Foundation[2020-CMKYGG-05] ; Chinese Academy of Sciences grant[XDA12010317] ; Natural Science Foundation of Shanghai[18ZR1447700] ; National Natural Science Foundation[31770796] ; National Science and Technology Major Project[2018ZX09711002-002-002] ; National Institute of Mental Health (NIMH) Psychoactive Drug Screening Program ; 100 Talents Program of the Chinese Academy of Sciences ; State Key Lab of Bioorganic and Natural Products Chemistry ; [RO1MH112205]
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology
语种英语
出版者CELL PRESS
WOS记录号WOS:000632670800006
源URL[http://119.78.100.183/handle/2S10ELR8/295287]  
专题新药研究国家重点实验室
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
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-+.

入库方式： OAI收割

来源：上海药物研究所

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