Structural genomics of the human dopamine receptor system
文献类型：期刊论文
| 作者 | Xu, Peiyu9,11; Huang, Sijie11; Krumm, Brian E.1; Zhuang, Youwen11; Mao, Chunyou2,3; Zhang, Yumu4,5,11; Wang, Yue4,11; Huang, Xi-Ping1; Liu, Yong-Feng1; He, Xinheng4,11 |
| 刊名 | CELL RESEARCH
 |
| 出版日期 | 2023-05-23 |
| 页码 | 13 |
| ISSN号 | 1001-0602 |
| DOI | 10.1038/s41422-023-00808-0 |
| 通讯作者 | Zhang, Yan(zhang_yan@zju.edu.cn) ; Roth, Bryan L.(bryan_roth@med.unc.edu) ; Xu, H. Eric(eric.xu@simm.ac.cn) |
| 英文摘要 | 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. |
| WOS关键词 | CRYO-EM STRUCTURE ; MOLECULAR-BASIS ; RECOGNITION ; VALIDATION ; ROTIGOTINE |
| 资助项目 | National Key R&D Programs of China[2018YFA0507002] ; Shanghai Municipal Science and Technology Major Project[2019SHZDZX02] ; Shanghai Municipal Science and Technology Major Project[XDB08020303] ; National Key Basic Research Program of China[2019YFA0508800] ; Key R&D Projects of Zhejiang Province[2021C03039] ; Fundamental Research Funds for the Central Universities[2019XZZX001-01-06] ; Zhejiang Province Natural Science Fund for Excellent Young Scholars[LR22C050002] ; National Natural Science Foundation of China[31770796] ; National Natural Science Foundation of China[32100959] ; National Science and Technology Major Project[2018ZX09711002] ; NIMH Psychoactive Drug Screening Program[RO1MH112205] ; Special Research Assistant Project of Chinese Academy of Sciences |
| WOS研究方向 | Cell Biology |
| 语种 | 英语 |
| 出版者 | SPRINGERNATURE |
| WOS记录号 | WOS:000994132000002 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306608]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zhang, Yan; Roth, Bryan L.; Xu, H. Eric |
| 作者单位 | 1.Univ North Carolina Chapel Hill, Dept Pharmacol, Med Sch, Chapel Hill, NC 27599 USA 2.Zhejiang Univ, Sir Run Run Shaw Hosp, Ctr Struct Pharmacol & Therapeut Dev, Sch Med, Hangzhou, Zhejiang, Peoples R China 3.Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Gen Surg, Sch Med, Hangzhou, Zhejiang, Peoples R China 4.Univ Chinese Acad Sci, Beijing, Peoples R China 5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 6.Zhejiang Univ, Sch Med, Dept Biophys, Sir Run Run Shaw Hosp, Hangzhou, Zhejiang, Peoples R China 7.Zhejiang Univ, MOE Frontier Sci Ctr Brain Res & Brain Machine Int, Sch Med, Hangzhou, Zhejiang, Peoples R China 8.Zhejiang Univ, Liangzhu Lab, Med Ctr, Hangzhou, Zhejiang, Peoples R China 9.MIT, McGovern Inst Brain Res, Cambridge, MA USA 10.Zhejiang Univ, Dept Pathol, Sir Run Run Shaw Hosp, Sch Med, Hangzhou, Zhejiang, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xu, Peiyu,Huang, Sijie,Krumm, Brian E.,et al. Structural genomics of the human dopamine receptor system[J]. CELL RESEARCH,2023:13. |
| APA | Xu, Peiyu.,Huang, Sijie.,Krumm, Brian E..,Zhuang, Youwen.,Mao, Chunyou.,...&Xu, H. Eric.(2023).Structural genomics of the human dopamine receptor system.CELL RESEARCH,13. |
| MLA | Xu, Peiyu,et al."Structural genomics of the human dopamine receptor system".CELL RESEARCH (2023):13. |
入库方式： OAI收割
来源：上海药物研究所
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