Recognition of methamphetamine and other amines by trace amine receptor TAAR1
文献类型：期刊论文
| 作者 | Liu, Heng1; Zheng, You2; Wang, Yue1,3; Wang, Yumeng3,4; He, Xinheng1,3; Xu, Peiyu1,3; Huang, Sijie1,3; Yuan, Qingning1,5; Zhang, Xinyue1,6; Wang, Ling2 |
| 刊名 | NATURE
 |
| 出版日期 | 2023-12-21 |
| 卷号 | 624期号:7992页码:663-+ |
| ISSN号 | 0028-0836 |
| DOI | 10.1038/s41586-023-06775-1 |
| 英文摘要 | Trace amine-associated receptor 1 (TAAR1), the founding member of a nine-member family of trace amine receptors, is responsible for recognizing a range of biogenic amines in the brain, including the endogenous beta-phenylethylamine (beta-PEA)1 as well as methamphetamine2, an abused substance that has posed a severe threat to human health and society3. Given its unique physiological role in the brain, TAAR1 is also an emerging target for a range of neurological disorders including schizophrenia, depression and drug addiction2,4,5. Here we report structures of human TAAR1-G-protein complexes bound to methamphetamine and beta-PEA as well as complexes bound to RO5256390, a TAAR1-selective agonist, and SEP-363856, a clinical-stage dual agonist for TAAR1 and serotonin receptor 5-HT1AR (refs. 6,7). Together with systematic mutagenesis and functional studies, the structures reveal the molecular basis of methamphetamine recognition and underlying mechanisms of ligand selectivity and polypharmacology between TAAR1 and other monoamine receptors. We identify a lid-like extracellular loop 2 helix/loop structure and a hydrogen-bonding network in the ligand-binding pockets, which may contribute to the ligand recognition in TAAR1. These findings shed light on the ligand recognition mode and activation mechanism for TAAR1 and should guide the development of next-generation therapeutics for drug addiction and various neurological disorders. We report on the structures of the TAAR1-G-protein complex when bound to methamphetamine and other amines. |
| WOS关键词 | METABOLISM ; TYPE-1 |
| 资助项目 | Ministry of Science and Technology of China[2018YFA0507002] ; Ministry of Science and Technology of China[2020YFA0509102] ; National Natural Science Foundation of China[32071194] ; National Natural Science Foundation of China[32130022] ; National Natural Science Foundation of China[82121005] ; National Natural Science Foundation of China[52272087] ; National Natural Science Foundation of China[82225025] ; National Natural Science Foundation of China[32071197] ; Shanghai Municipal Science and Technology Major Project[2019SHZDZX02] ; CAS Strategic Priority Research Programme[XDB37030103] ; Lingang Laboratory[LG-GG-202204-01] ; National Key R&D Program of China[2022YFC2703105] ; Shanghai Institute of Material Medica ; Bio-EM platform of ShanghaiTech University ; Shanghai Frontiers Science Center for Biomacromolecules and Precision Medicine at ShanghaiTech University |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| 出版者 | NATURE PORTFOLIO |
| WOS记录号 | WOS:001128871300021 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309572]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Liu, Wenbin; Wang, Sheng; Xu, H. Eric; Xu, Fei |
| 作者单位 | 1.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 3.Univ Chinese Acad Sci, Beijing, Peoples R China 4.Chinese Acad Sci, Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Adv Electron Microscope Ctr, Shanghai, Peoples R China 6.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Peoples R China 7.Shanghai Res Inst Criminal Sci & Technol, Shanghai Key Lab Crime Scene Evidence, Shanghai, Peoples R China 8.Shanghai Yuansi Stand Sci & Technol Co Ltd, Shanghai 200072, Peoples R China 9.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Life Sci, Key Lab Syst Hlth Sci Zhejiang Prov, Hangzhou, Peoples R China 10.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Heng,Zheng, You,Wang, Yue,et al. Recognition of methamphetamine and other amines by trace amine receptor TAAR1[J]. NATURE,2023,624(7992):663-+. |
| APA | Liu, Heng.,Zheng, You.,Wang, Yue.,Wang, Yumeng.,He, Xinheng.,...&Xu, Fei.(2023).Recognition of methamphetamine and other amines by trace amine receptor TAAR1.NATURE,624(7992),663-+. |
| MLA | Liu, Heng,et al."Recognition of methamphetamine and other amines by trace amine receptor TAAR1".NATURE 624.7992(2023):663-+. |
入库方式： OAI收割
来源：上海药物研究所
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