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Molecular recognition of formylpeptides and diverse agonists by the formylpeptide receptors FPR1 and FPR2

文献类型：期刊论文

作者Zhuang, Youwen2; Wang, Lei1; Guo, Jia2,3; Sun, Dapeng1; Wang, Yue2,3; Liu, Weiyi2,3; Xu, H. Eric2,3; Zhang, Cheng1
刊名NATURE COMMUNICATIONS
出版日期2022-02-25
卷号13期号:1页码:12
DOI10.1038/s41467-022-28586-0
通讯作者Xu, H. Eric(Eric.Xu@simm.ac.cn) ; Zhang, Cheng(chengzh@pitt.edu)
英文摘要Zhuang et al. report four cryo-EM structures of formylpeptide receptors FPR1 and FPR2 coupled with Gi protein and diverse agonists, revealing how FPRs as pattern recognition receptors recognize formylpeptides and synthetic agonists and a distinctive receptor activation mechanism. The formylpeptide receptors (FPRs) mediate pattern recognition of formylated peptides derived from invading pathogens or mitochondria from dead host cells. They can also sense other structurally distinct native peptides and even lipid mediators to either promote or resolve inflammation. Pharmacological targeting of FPRs represents a novel therapeutic approach in treating inflammatory diseases. However, the molecular mechanisms underlying FPR ligand recognition are elusive. We report cryo-EM structures of G(i)-coupled FPR1 and FPR2 bound to a formylpeptide and G(i)-coupled FPR2 bound to two synthetic peptide and small-molecule agonists. Together with mutagenesis data, our structures reveal the molecular mechanism of formylpeptide recognition by FPRs and structural variations of FPR1 and FPR2 leading to their different ligand preferences. Structural analysis also suggests that diverse FPR agonists sample a conserved activation chamber at the bottom of ligand-binding pockets to activate FPRs. Our results provide a basis for rational drug design on FPRs.
WOS关键词FORMYL-PEPTIDE RECEPTORS ; PRO-RESOLVING MEDIATORS ; STRUCTURAL INSIGHTS ; INFLAMMATION ; RESOLUTION ; LIGAND ; DETERMINANTS ; RESPONSES
资助项目Ministry of Science and Technology (China)[2018YFA0507002] ; Shanghai Municipal Science and Technology Major Project[2019SHZDZX02] ; CAS Strategic Priority Research Program[XDB08020303] ; Special Research Assistant Project of Chinese Academy of Sciences[E1G707R078] ; National Institutes of Health (NIH)[1R03TR003306-01] ; National Institutes of Health (NIH)[1R35GM128641]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000771121400004
出版者NATURE PORTFOLIO
源URL[http://119.78.100.183/handle/2S10ELR8/300027]  
专题中国科学院上海药物研究所
通讯作者Xu, H. Eric; Zhang, Cheng
作者单位1.Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15261 USA
2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714		 Zhuang, Youwen,Wang, Lei,Guo, Jia,et al. Molecular recognition of formylpeptides and diverse agonists by the formylpeptide receptors FPR1 and FPR2[J]. NATURE COMMUNICATIONS,2022,13(1):12.
APA Zhuang, Youwen.,Wang, Lei.,Guo, Jia.,Sun, Dapeng.,Wang, Yue.,...&Zhang, Cheng.(2022).Molecular recognition of formylpeptides and diverse agonists by the formylpeptide receptors FPR1 and FPR2.NATURE COMMUNICATIONS,13(1),12.
MLA Zhuang, Youwen,et al."Molecular recognition of formylpeptides and diverse agonists by the formylpeptide receptors FPR1 and FPR2".NATURE COMMUNICATIONS 13.1(2022):12.

入库方式： OAI收割

来源：上海药物研究所

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