Structure of formylpeptide receptor 2-G(i) complex reveals insights into ligand recognition and signaling

doi:10.1038/s41467-020-14728-9

	Structure of formylpeptide receptor 2-G(i) complex reveals insights into ligand recognition and signaling
	Zhuang, Youwen 4,5,6; Liu, Heng 7; Zhou, X. Edward 6; Verma, Ravi Kumar 8; de Waal, Parker W.6; Jang, Wonjo 1; Xu, Ting-Hai 6; Wang, Lei 7; Meng, Xing 2; Zhao, Gongpu 2
刊名	NATURE COMMUNICATIONS
	2020-02-14
卷号	11 期号:1 页码:12
ISSN号	2041-1723
DOI	10.1038/s41467-020-14728-9
通讯作者	Xu, H. Eric(Eric.Xu@simm.ac.cn) ; Zhang, Cheng(chengzh@pitt.edu)
英文摘要	Formylpeptide receptors (FPRs) as G protein-coupled receptors (GPCRs) can recognize formylpeptides derived from pathogens or host cells to function in host defense and cell clearance. In addition, FPRs, especially FPR2, can also recognize other ligands with a large chemical diversity generated at different stages of inflammation to either promote or resolve inflammation in order to maintain a balanced inflammatory response. The mechanism underlying promiscuous ligand recognition and activation of FPRs is not clear. Here we report a cryo-EM structure of FPR2-G(i) signaling complex with a peptide agonist. The structure reveals a widely open extracellular region with an amphiphilic environment for ligand binding. Together with computational docking and simulation, the structure suggests a molecular basis for the recognition of formylpeptides and a potential mechanism of receptor activation, and reveals conserved and divergent features in G(i) coupling. Our results provide a basis for understanding the molecular mechanism of the functional promiscuity of FPRs.
资助项目	National Institutes of Health grants[1R35GM128641] ; National Institutes of Health grants[1R01GM127710] ; National Institutes of Health grants[1R01GM130142] ; Van Andel Research Institute[XDB08020303] ; Biomedical Research Council of A*STAR including the Industry Alignment Fund Pre-Positioning[H18/01/a0/C14] ; UCAS joint Ph.D. Training Program
WOS关键词	FORMYL-PEPTIDE RECEPTOR ; PROTEIN-COUPLED RECEPTORS ; VAL-D-MET ; ACTIVATES NEUTROPHILS ; PATTERN-RECOGNITION ; AGONIST ; IDENTIFICATION ; INFLAMMATION ; RESOLUTION ; DATABASE
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000564260600002
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/291595]
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.Augusta Univ, Med Coll Georgia, Dept Pharmacol & Toxicol, Augusta, GA 30912 USA 2.Van Andel Res Inst, David Van Andel Adv Cryoelectron Microscopy Suite, Grand Rapids, MI 49503 USA 3.Takeda Res, 9625 Towne Ctr Dr, San Diego, CA 92130 USA 4.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 6.Van Andel Res Inst, Program Struct Biol, Ctr Canc & Cell Biol, Grand Rapids, MI 49503 USA 7.Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Lab GPCR Biol, Pittsburgh, PA 15261 USA 8.ASTAR, Bioinformat Inst BII, Singapore, Singapore
推荐引用方式 GB/T 7714	Zhuang, Youwen,Liu, Heng,Zhou, X. Edward,et al. Structure of formylpeptide receptor 2-G(i) complex reveals insights into ligand recognition and signaling[J]. NATURE COMMUNICATIONS,2020,11(1):12.
APA	Zhuang, Youwen.,Liu, Heng.,Zhou, X. Edward.,Verma, Ravi Kumar.,de Waal, Parker W..,...&Zhang, Cheng.(2020).Structure of formylpeptide receptor 2-G(i) complex reveals insights into ligand recognition and signaling.NATURE COMMUNICATIONS,11(1),12.
MLA	Zhuang, Youwen,et al."Structure of formylpeptide receptor 2-G(i) complex reveals insights into ligand recognition and signaling".NATURE COMMUNICATIONS 11.1(2020):12.