Structures of the entire human opioid receptor family

doi:10.1016/j.cell.2022.12.026

	Structures of the entire human opioid receptor family
	Wang, Yue 1,2; Zhuang, Youwen 1; DiBerto, Jeffrey F.3; Zhou, X. Edward 4; Schmitz, Gavin P.3; Yuan, Qingning 1,5; Jain, Manish K.3; Liu, Weiyi 1,2; Melcher, Karsten 4; Jiang, Yi 1,6; Roth, Bryan L.3; Xu, H. Eric1,2,7
	2023-01-19
发表期刊	CELL; (IF:45.5[JCR-2023],49.0[5-Year])
ISSN	0092-8674
EISSN	1097-4172
卷号	186 期号:2 页码:413-427.e17
DOI	10.1016/j.cell.2022.12.026
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 (μOR, δOR, κOR, 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 β-endorphin- and endomorphin-bound μOR, deltorphin-bound δOR, dynorphin-bound κOR, 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.
关键词	analgesics deltorphin dynorphin endogenous opioid peptides endomorphin endorphin GPCRs ligand selectivity nociceptin opioid receptors
学科门类	Biochemistry, Genetics and Molecular Biology (all)
URL	查看原文
收录类别	SCOPUS
语种	英语
原始文献类型	Article
Scopus 记录号	2-s2.0-85146263920
来源库	SCOPUS
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/286441
专题	生命科学与技术学院生命科学与技术学院_特聘教授组_徐华强组
作者单位	1.The CAS Key Laboratory of Receptor Research and the State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai,201203,China; 2.University of Chinese Academy of Sciences,Beijing,100049,China; 3.Department of Pharmacology,University of North Carolina at Chapel Hill School of Medicine,Chapel Hill,27599,United States; 4.Department of Structural Biology,Van Andel Research Institute,Grand Rapids,49503,United States; 5.The Shanghai Advanced Electron Microscope Center,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai,201203,China; 6.Lingang Laboratory,Shanghai,200031,China; 7.School of Life Science and Technology,ShanghaiTech University,Shanghai,201210,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):413-427.e17.
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),413-427.e17.
MLA	Wang, Yue,et al."Structures of the entire human opioid receptor family".CELL; 186.2(2023):413-427.e17.