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  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 国家级研究中心
  5. 原创新药研究全国重点实验室
Molecular insights into ligand recognition and receptor activation of GPR15

文献类型：期刊论文

作者Chen, Shutian1,2; Han, Xuteng1,2; Zhang, Yuxia1,2; Ma, Limin1; Yi, Cuiying1; Chu, Xiaojing1; Tan, Qiuxiang1; Han, Shuo1,2; Zhao, Qiang1,2,3; Wu, Beili1,2,4,5,6
刊名ISCIENCE
出版日期2025-12-19
卷号28期号:12页码:16
DOI10.1016/j.isci.2025.113935
英文摘要In response to the chemokine-like peptide GPR15L, G protein-coupled receptor 15 (GPR15) is crucial for immune cell trafficking and inflammatory diseases. However, understanding of its physiology and pathology is hindered by lack of molecular details of the interaction between GPR15 and the full-length GPR15L. Here, we report the structure of GPR15 bound to the full-length GPR15L and Gi3 protein. Combined with mutagenesis data, this structure reveals key interactions that define ligand recognition and a subpocket that governs GPR15L selectivity and receptor activation. Molecular dynamics simulations suggest that sulfation modifications in the N-terminal region of GPR15 may play a role in stabilizing the binding between GPR15 and the core region of GPR15L. Furthermore, molecular docking of some potential small-molecule antagonists suggests a conserved molecular pattern of these ligands inhibiting receptor activation. These findings provide essential insight into functional modulation of GPR15 and would facilitate development of therapeutic strategies for treatment of inflammation and immune diseases.
WOS关键词PROTEIN ; VISUALIZATION ; MOLPROBITY ; CHEMOKINE ; SOFTWARE ; SYSTEM
资助项目National Key R&D Program of China[2022YFA 1302900] ; CAS Project for Young Scientists in Basic Research[YSBR-106] ; National Science Foundation of China[82121005] ; 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]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:001618754900001
出版者CELL PRESS
源URL[http://119.78.100.183/handle/2S10ELR8/322031]  
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Han, Shuo; Zhao, Qiang; Wu, Beili
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, State Key Lab Drug Res, Shanghai 201203, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China
4.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310020, Peoples R China
5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Acad Nat Sci, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Chen, Shutian,Han, Xuteng,Zhang, Yuxia,et al. Molecular insights into ligand recognition and receptor activation of GPR15[J]. ISCIENCE,2025,28(12):16.
APA Chen, Shutian.,Han, Xuteng.,Zhang, Yuxia.,Ma, Limin.,Yi, Cuiying.,...&Wu, Beili.(2025).Molecular insights into ligand recognition and receptor activation of GPR15.ISCIENCE,28(12),16.
MLA Chen, Shutian,et al."Molecular insights into ligand recognition and receptor activation of GPR15".ISCIENCE 28.12(2025):16.

入库方式： OAI收割

来源：上海药物研究所

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