Ligand-induced activation and G protein coupling of prostaglandin F-2 alpha receptor

doi:10.1038/s41467-023-38411-x

	Ligand-induced activation and G protein coupling of prostaglandin F-2 alpha receptor
	Wu, Canrong 1; Xu, Youwei 1; He, Qian 1; Li, Dianrong 2; Duan, Jia 1; Li, Changyao3,4 ; You, Chongzhao 1; Chen, Han 5; Fan, Weiliang 2; Jiang, Yi3,4 ; Eric Xu, H.1,6
	2023-05-09
发表期刊	NATURE COMMUNICATIONS (IF:14.7[JCR-2023],16.1[5-Year])
EISSN	2041-1723
卷号	14 期号:1
发表状态	已发表
DOI	10.1038/s41467-023-38411-x
摘要	Prostaglandin F-2 alpha (PGF(2 alpha)), an endogenous arachidonic acid metabolite, regulates diverse physiological functions in many tissues and cell types through binding and activation of a G-protein-coupled receptor (GPCR), the PGF(2 alpha) receptor (FP), which also is the primary therapeutic target for glaucoma and several other diseases. Here, we report cryo-electron microscopy (cryo-EM) structures of the human FP bound to endogenous ligand PGF(2 alpha) and anti-glaucoma drugs LTPA and TFPA at global resolutions of 2.67 angstrom, 2.78 angstrom, and 3.14 angstrom. These structures reveal distinct features of FP within the lipid receptor family in terms of ligand binding selectivity, its receptor activation, and G protein coupling mechanisms, including activation in the absence of canonical PIF and ERY motifs and G(q) coupling through direct interactions with receptor transmembrane helix 1 and intracellular loop 1. Together with mutagenesis and functional studies, our structures reveal mechanisms of ligand recognition, receptor activation, and G protein coupling by FP, which could facilitate rational design of FP-targeting drugs. Prostaglandin F-2 alpha receptor (FP) is the primary therapeutic target for glaucoma and several other diseases. Here, the authors reveal structural mechanisms of ligand recognition, receptor activation, and G protein coupling by FP.
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收录类别	SCI
语种	英语
资助项目	Ministry of Science and Technology (China)[2018YFA0507002] ; Shanghai Municipal Science and Technology Major Project[2019SHZDZX02] ; CAS Strategic Priority Research Program[XDB37030103] ; National Natural Science Foundation of China["81902085","32130022","82121005","32171187"] ; China Postdoctoral Science Foundation[2021M703342] ; Shanghai Post-doctoral Excellence Program[2021429] ; Key tasks of Lingang Laboratory[LG202101-01-03]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:001053796300027
出版者	NATURE PORTFOLIO
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/327928
专题	生命科学与技术学院_博士生生命科学与技术学院
通讯作者	Wu, Canrong; Eric Xu, H.
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Medica, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Sironax Beijing Co Ltd, Beijing 102206, Peoples R China 3.Lingang Lab, Shanghai 200031, Peoples R China 4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 5.Fujian Med Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Fuzhou 350108, Fujian, Peoples R China 6.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Wu, Canrong,Xu, Youwei,He, Qian,et al. Ligand-induced activation and G protein coupling of prostaglandin F-2 alpha receptor[J]. NATURE COMMUNICATIONS,2023,14(1).
APA	Wu, Canrong.,Xu, Youwei.,He, Qian.,Li, Dianrong.,Duan, Jia.,...&Eric Xu, H..(2023).Ligand-induced activation and G protein coupling of prostaglandin F-2 alpha receptor.NATURE COMMUNICATIONS,14(1).
MLA	Wu, Canrong,et al."Ligand-induced activation and G protein coupling of prostaglandin F-2 alpha receptor".NATURE COMMUNICATIONS 14.1(2023).