Structural basis for ligand recognition of the neuropeptide Y Y-2 receptor

doi:10.1038/s41467-021-21030-9

	Structural basis for ligand recognition of the neuropeptide Y Y-2 receptor
	Tang, Tingting 1,2,3; Hartig, Christin 4; Chen, Qiuru 1,3,5; Zhao, Wenli 1,2,3; Kaiser, Anette 4; Zhang, Xuefeng 1,2,3; Zhang, Hui 1,2,3; Qu, Honge 1,3,5; Yi, Cuiying 1; Ma, Limin 2
刊名	NATURE COMMUNICATIONS
	2021-02-02
卷号	12 期号:1 页码:9
ISSN号	2041-1723
DOI	10.1038/s41467-021-21030-9
通讯作者	Zhao, Qiang(zhaoq@simm.ac.cn) ; Beck-Sickinger, Annette G.(abeck-sickinger@uni-leipzig.de) ; Wu, Beili(beiliwu@simm.ac.cn)
英文摘要	The human neuropeptide Y (NPY) Y-2 receptor (Y2R) plays essential roles in food intake, bone formation and mood regulation, and has been considered an important drug target for obesity and anxiety. However, development of drugs targeting Y2R remains challenging with no success in clinical application yet. Here, we report the crystal structure of Y2R bound to a selective antagonist JNJ-31020028 at 2.8 angstrom resolution. The structure reveals molecular details of the ligand-binding mode of Y2R. Combined with mutagenesis studies, the Y2R structure provides insights into key factors that define antagonistic activity of diverse antagonists. Comparison with the previously determined antagonist-bound Y1R structures identified receptor-ligand interactions that play different roles in modulating receptor activation and mediating ligand selectivity. These findings deepen our understanding about molecular mechanisms of ligand recognition and subtype specificity of NPY receptors, and would enable structure-based drug design. The human neuropeptide Y receptor Y-2 (Y2R) is a drug target for the treatment of obesity and anxiety. Crystal structure of Y2R bound to a selective antagonist and accompanying mutagenesis provide insights into ligand recognition and subtype specificity of NPY receptors.
资助项目	National Science Foundation of China[31825010] ; National Science Foundation of China[31700653] ; National Key R&D Program of China[2018YFA0507000] ; German Research Foundation[421152132] ; German Research Foundation[CRC 1423] ; CAS Strategic Priority Research Program[XDB37030100] ; Shanghai Science and Technology Committee[19JC1416200] ; Shanghai Science and Technology Committee[18XD1404800]
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE RESEARCH
WOS记录号	WOS:000617063000007
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/295821]
专题	中国科学院上海药物研究所
通讯作者	Zhao, Qiang; Beck-Sickinger, Annette G.; Wu, Beili
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 4.Univ Leipzig, Inst Biochem, Fac Life Sci, Bruderstr 34, D-04103 Leipzig, Germany 5.ShanghaiTech Univ, Sch Life Sci & Technol, 393 Hua Xia Zhong Rd, Shanghai 201210, Peoples R China 6.Chinese Acad Sci, CAS Ctr Excellence Biomacromol, Beijing 100101, Peoples R China 7.UCAS, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China
推荐引用方式 GB/T 7714	Tang, Tingting,Hartig, Christin,Chen, Qiuru,et al. Structural basis for ligand recognition of the neuropeptide Y Y-2 receptor[J]. NATURE COMMUNICATIONS,2021,12(1):9.
APA	Tang, Tingting.,Hartig, Christin.,Chen, Qiuru.,Zhao, Wenli.,Kaiser, Anette.,...&Wu, Beili.(2021).Structural basis for ligand recognition of the neuropeptide Y Y-2 receptor.NATURE COMMUNICATIONS,12(1),9.
MLA	Tang, Tingting,et al."Structural basis for ligand recognition of the neuropeptide Y Y-2 receptor".NATURE COMMUNICATIONS 12.1(2021):9.