Structural basis of ligand binding modes at the human formyl peptide receptor 2

doi:10.1038/s41467-020-15009-1

	Structural basis of ligand binding modes at the human formyl peptide receptor 2
	Chen, Tong 2,3,4; Xiong, Muya 2,4; Zong, Xin 2,3,4; Ge, Yunjun 5; Zhang, Hui 2,3,4; Wang, Mu 2,6; Won Han, Gye 7; Yi, Cuiying 2; Ma, Limin 3; Ye, Richard D.1
刊名	NATURE COMMUNICATIONS
	2020-03-05
卷号	11 期号:1 页码:9
ISSN号	2041-1723
DOI	10.1038/s41467-020-15009-1
通讯作者	Xu, Yechun(ycxu@simm.ac.cn) ; Zhao, Qiang(zhaoq@simm.ac.cn) ; Wu, Beili(beiliwu@simm.ac.cn)
英文摘要	The human formyl peptide receptor 2 (FPR2) plays a crucial role in host defense and inflammation, and has been considered as a drug target for chronic inflammatory diseases. A variety of peptides with different structures and origins have been characterized as FPR2 ligands. However, the ligand-binding modes of FPR2 remain elusive, thereby limiting the development of potential drugs. Here we report the crystal structure of FPR2 bound to the potent peptide agonist WKYMVm at 2.8 angstrom resolution. The structure adopts an active conformation and exhibits a deep ligand-binding pocket. Combined with mutagenesis, ligand binding and signaling studies, key interactions between the agonist and FPR2 that govern ligand recognition and receptor activation are identified. Furthermore, molecular docking and functional assays reveal key factors that may define binding affinity and agonist potency of formyl peptides. These findings deepen our understanding about ligand recognition and selectivity mechanisms of the formyl peptide receptor family. Formyl peptide receptors (FPRs) are GPCRs that play important roles in transducing chemotactic signals in phagocytes and mediating host-defense and inflammatory responses. Here the authors present the 2.8 angstrom crystal structure of human FPR2 in complex with the peptide agonist WKYMVm and in combination with molecular docking, ligand-binding and signalling assays provide further insights into the binding modes of FPR2 to both non-formyl and formyl peptides.
资助项目	National Key R&D Programs of China[2018YFA0507000] ; National Key R&D Programs of China[2016YFA0502301] ; National Science Foundation of China[31825010] ; National Science Foundation of China[31730027] ; National Science Foundation of China[81525024] ; CAS Strategic Priority Research Program[XDB37000000] ; Key Research Program of Frontier Sciences, CAS[QYZDB-SSW-SMC024] ; Key Research Program of Frontier Sciences, CAS[QYZDB-SSW-SMC054] ; National Science & Technology Major Project-Key New Drug Creation and Manufacturing Program, China[2018ZX09711002]
WOS关键词	CRYSTAL-STRUCTURE ; PROTEIN ; AGONIST ; STIMULATION ; MET
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000543997700014
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/291856]
专题	中国科学院上海药物研究所
通讯作者	Xu, Yechun; Zhao, Qiang; Wu, Beili
作者单位	1.Chinese Univ Hong Kong, Sch Life & Hlth Sci, Shenzhen 518172, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 4.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 5.Univ Macau, Inst Chinese Med Sci, Macau 999078, Peoples R China 6.ShanghaiTech Univ, Sch Life Sci & Technol, 393 Hua Xia Zhong Rd, Shanghai 201210, Peoples R China 7.Univ Southern Calif, Bridge Inst Michelson Ctr Convergent Biosci, Dept Chem, 1002 West Childs Way, Los Angeles, CA 90089 USA
推荐引用方式 GB/T 7714	Chen, Tong,Xiong, Muya,Zong, Xin,et al. Structural basis of ligand binding modes at the human formyl peptide receptor 2[J]. NATURE COMMUNICATIONS,2020,11(1):9.
APA	Chen, Tong.,Xiong, Muya.,Zong, Xin.,Ge, Yunjun.,Zhang, Hui.,...&Wu, Beili.(2020).Structural basis of ligand binding modes at the human formyl peptide receptor 2.NATURE COMMUNICATIONS,11(1),9.
MLA	Chen, Tong,et al."Structural basis of ligand binding modes at the human formyl peptide receptor 2".NATURE COMMUNICATIONS 11.1(2020):9.