Structures of the entire human opioid receptor family
文献类型：期刊论文
| 作者 | Wang, Yue2,3,4; Zhuang, Youwen2,3; DiBerto, Jeffrey F.5; Zhou, X. Edward1; Schmitz, Gavin P.5; Yuan, Qingning2,3,6; Jain, Manish K.5; Liu, Weiyi2,3,4; Melcher, Karsten1; Jiang, Yi2,3,7
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| 刊名 | CELL
 |
| 出版日期 | 2023-01-19 |
| 卷号 | 186期号:2页码:413-+ |
| ISSN号 | 0092-8674 |
| DOI | 10.1016/j.cell.2022.12.026 |
| 通讯作者 | Zhuang, Youwen(zhuangyouwen@simm.ac.cn) ; Roth, Bryan L.(bryan_roth@med.unc.edu) ; Xu, H. Eric(eric.xu@simm.ac.cn) |
| 英文摘要 | Opioids are effective analgesics, but their use is beset by serious side effects, including addiction and respiratory depression, which contribute to the ongoing opioid crisis. The human opioid system contains four opioid receptors (mOR, dOR, kOR, and NOPR) and a set of related endogenous opioid peptides (EOPs), which show distinct selectivity toward their respective opioid receptors (ORs). Despite being key to the development of safer analgesics, the mechanisms of molecular recognition and selectivity of EOPs to ORs remain unclear. Here, we systematically characterize the binding of EOPs to ORs and present five structures of EOP-OR-Gi complexes, including b-endorphin- and endomorphin-bound mOR, deltorphin-bound dOR, dynorphin-bound kOR, and nociceptin-bound NOPR. These structures, supported by biochemical results, uncover the specific recognition and selectivity of opioid peptides and the conserved mechanism of opioid receptor activation. These results provide a structural framework to facilitate rational design of safer opioid drugs for pain relief. |
| WOS关键词 | NOCICEPTIN/ORPHANIN FQ RECEPTOR ; PEPTIDE RECOGNITION ; ACTIVE STATE ; ANALGESICS ; INSIGHTS ; BINDING ; ACTIVATION ; MECHANISM ; COMPLEX ; ANTINOCICEPTION |
| 资助项目 | Ministry of Science and Technology (China)[2018YFA0507002] ; National Natural Science Foundation of China[82121005] ; National Natural Science Foundation of China[32130022] ; National Natural Science Foundation of China[32171187] ; Shanghai Municipal Science and Technology Major Project[2019SHZDZX02] ; CAS Strategic Priority Research Program[XDB37030103] ; Special Research Assistant Project of Chinese Academy of Sciences ; Michael Hooker Distinguished Professorship ; NIMH Psychoactive Drug Screening Program ; NIH[RO1DA055656] ; Shanghai Municipal Science and Technology Major Project |
| WOS研究方向 | Biochemistry & Molecular Biology ; Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:001018360200001 |
| 出版者 | CELL PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306388]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zhuang, Youwen; Roth, Bryan L.; Xu, H. Eric |
| 作者单位 | 1.Van Andel Res Inst, Dept Biol Struct, Grand Rapids, MI 49503 USA 2.Chinese Acad Sci, CAS Key Lab Receptor Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 5.Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA 6.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Adv Electron Microscope Ctr, Shanghai 201203, Peoples R China 7.Lingang Lab, Shanghai 200031, Peoples R China 8.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Yue,Zhuang, Youwen,DiBerto, Jeffrey F.,et al. Structures of the entire human opioid receptor family[J]. CELL,2023,186(2):413-+. |
| APA | Wang, Yue.,Zhuang, Youwen.,DiBerto, Jeffrey F..,Zhou, X. Edward.,Schmitz, Gavin P..,...&Xu, H. Eric.(2023).Structures of the entire human opioid receptor family.CELL,186(2),413-+. |
| MLA | Wang, Yue,et al."Structures of the entire human opioid receptor family".CELL 186.2(2023):413-+. |
入库方式： OAI收割
来源：上海药物研究所
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