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  2. 上海药物研究所
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  4. 新药研究国家重点实验室
Ligand-induced activation and G protein coupling of prostaglandin F-2 alpha receptor

文献类型：期刊论文

作者Wu, Canrong1; Xu, Youwei1; He, Qian1; Li, Dianrong2; Duan, Jia1; Li, Changyao3,4; You, Chongzhao1; Chen, Han5; Fan, Weiliang2; Jiang, Yi3,4
刊名NATURE COMMUNICATIONS
出版日期2023-05-09
卷号14期号:1页码:11
DOI10.1038/s41467-023-38411-x
通讯作者Wu, Canrong(wucanrong@simm.ac.cn) ; Eric Xu, H.(eric.xu@simm.ac.cn)
英文摘要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.
WOS关键词OPEN-ANGLE GLAUCOMA ; LATANOPROST ; TAFLUPROST ; ANALOGS ; STABILIZATION ; LOCALIZATION ; EXPRESSION ; EFFICACY ; CLONING ; CDNA
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] ; National Natural Science Foundation of China[32130022] ; National Natural Science Foundation of China[82121005] ; National Natural Science Foundation of China[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
语种英语
WOS记录号WOS:001053796300027
出版者NATURE PORTFOLIO
源URL[http://119.78.100.183/handle/2S10ELR8/307013]  
专题新药研究国家重点实验室
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):11.
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),11.
MLA Wu, Canrong,et al."Ligand-induced activation and G protein coupling of prostaglandin F-2 alpha receptor".NATURE COMMUNICATIONS 14.1(2023):11.

入库方式： OAI收割

来源：上海药物研究所

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