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  2. 上海药物研究所
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  5. 原创新药研究全国重点实验室
Noncanonical agonist-dependent and -independent arrestin recruitment of GPR1

文献类型：期刊论文

作者Cai, Heng4,5,6,7; Lin, Xiaowen3,5,6; Zhao, Lechen3,5; He, Maozhou3,5; Yu, Jie2,3,4; Zhang, Bingjie2; Ma, Yuandi3,6; Chang, Xiaohua3,5; Tang, Yuxuan3,5; Luo, Tianyu3,5
刊名SCIENCE
出版日期2025-11-20
卷号390期号:6775页码:15
ISSN号0036-8075
DOI10.1126/science.adt8794
英文摘要G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors have diverse signaling properties with differential preferences for downstream pathways. Certain receptors, such as the chemerin receptor GPR1, undergo arrestin-mediated internalization but weak G protein signaling. However, the mechanisms of this unusual signaling pattern and its physiological relevance are unclear. We report the structures of GPR1 bound to chemerin and beta-arrestin 1 or beta-arrestin 2 and an agonist-free GPR1-beta-arrestin 1 complex. Upon agonist stimulation, the receptor binds the two arrestins in distinct interaction patterns, which may account for their differential cellular responses. Agonist-independent internalization was mediated by an inactive, constitutively phosphorylated GPR1 that accommodates beta-arrestin 1 in an unconventional pocket together with a fatty acid, which potentially provides a basis for GPR1 modulating lipid accumulation in lipid-overloaded adipocytes.
WOS关键词CHEMERIN ; NOMENCLATURE ; ENDOCYTOSIS ; EXPRESSION ; RECEPTORS ; US28
资助项目National Key R&D Program of China[2022YFA1302900] ; National Science Foundation of China[82121005] ; National Science Foundation of China[32161133011] ; National Science Foundation of China[32401012] ; National Science Foundation of China[82521004] ; National Science Foundation of China[32471496] ; National Science Foundation of China[32301250] ; CAS Strategic Priority Research Program[XDB0830000] ; CAS Strategic Priority Research Program[XDB1060000] ; Shanghai Pilot Program for Basic Research-Chinese Academy of Sciences, Shanghai Branch[JCYJ-SHFY-2021-008] ; Shanghai Academy of Natural Sciences (SANS) Exploration Scholar ; Shanghai Science and Technology Development Foundation[22QA1412000] ; Zhejiang Provincial Natural Science Foundation of China[LQ24C050004] ; Hangzhou Institute for Advanced Study[2024HIAS-Y011] ; Shanghai Frontiers Science Center for Biomacromolecules and Precision Medicine at ShanghaiTech University
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:001621522600019
出版者AMER ASSOC ADVANCEMENT SCIENCE
源URL[http://119.78.100.183/handle/2S10ELR8/322196]  
专题国家级研究中心_原创新药研究全国重点实验室
通讯作者Xie, Cen; Shui, Wenqing; Zhao, Qiang; Zhu, Ya; Wu, Beili
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Acad Nat Sci SANS, Shanghai, Peoples R China
2.ShanghaiTech Univ, iHuman Inst, Shanghai, Peoples R China
3.Univ Chinese Acad Sci, Beijing, Peoples R China
4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
5.Univ Chinese Acad Sci, Sch Pharmaceut Sci & Technol, Hangzhou Inst Adv Study, Hangzhou, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, State Key Lab Drug Res, Shanghai, Peoples R China
7.Lingang Lab, Shanghai, Peoples R China
8.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan, Peoples R China
推荐引用方式
GB/T 7714		 Cai, Heng,Lin, Xiaowen,Zhao, Lechen,et al. Noncanonical agonist-dependent and -independent arrestin recruitment of GPR1[J]. SCIENCE,2025,390(6775):15.
APA Cai, Heng.,Lin, Xiaowen.,Zhao, Lechen.,He, Maozhou.,Yu, Jie.,...&Wu, Beili.(2025).Noncanonical agonist-dependent and -independent arrestin recruitment of GPR1.SCIENCE,390(6775),15.
MLA Cai, Heng,et al."Noncanonical agonist-dependent and -independent arrestin recruitment of GPR1".SCIENCE 390.6775(2025):15.

入库方式： OAI收割

来源：上海药物研究所

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