Cryo-EM structures of adenosine receptor A3AR bound to selective agonists
文献类型：期刊论文
| 作者 | Cai, Hongmin6; Guo, Shimeng6; Xu, Youwei6; Sun, Jun5,6; Li, Junrui6; Xia, Zhikan6; Jiang, Yi4; Xie, Xin1,2,3,5,6 ; Xu, H. Eric2,5,6
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| 刊名 | NATURE COMMUNICATIONS
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| 出版日期 | 2024-04-16 |
| 卷号 | 15期号:1页码:10 |
| DOI | 10.1038/s41467-024-47207-6 |
| 通讯作者 | Cai, Hongmin(caihongmin@simm.ac.cn) ; Xie, Xin(xxie@simm.ac.cn) ; Xu, H. Eric(eric.xu@simm.ac.cn) |
| 英文摘要 | The adenosine A(3) receptor (A(3)AR), a key member of the G protein-coupled receptor family, is a promising therapeutic target for inflammatory and cancerous conditions. The selective A(3)AR agonists, CF101 and CF102, are clinically significant, yet their recognition mechanisms remained elusive. Here we report the cryogenic electron microscopy structures of the full-length human A(3)AR bound to CF101 and CF102 with heterotrimeric G(i) protein in complex at 3.3-3.2 & Aring; resolution. These agonists reside in the orthosteric pocket, forming conserved interactions via their adenine moieties, while their 3-iodobenzyl groups exhibit distinct orientations. Functional assays reveal the critical role of extracellular loop 3 in A(3)AR's ligand selectivity and receptor activation. Key mutations, including His(3.37), Ser(5.42), and Ser(6.52), in a unique sub-pocket of A(3)AR, significantly impact receptor activation. Comparative analysis with the inactive A(2A)AR structure highlights a conserved receptor activation mechanism. Our findings provide comprehensive insights into the molecular recognition and signaling of A(3)AR, paving the way for designing subtype-selective adenosine receptor ligands. |
| WOS关键词 | MOLECULAR-CLONING ; N-6-BENZYLADENOSINE-5-URONAMIDES |
| 资助项目 | National Natural Science Foundation of China (National Science Foundation of China)[XDB37030103] ; CAS Strategic Priority Research Program[32301004] ; CAS Strategic Priority Research Program[82121005] ; CAS Strategic Priority Research Program[32130022] ; CAS Strategic Priority Research Program[82330113] ; CAS Strategic Priority Research Program[82304579] ; CAS Strategic Priority Research Program[32171187] ; National Natural Science Foundation of China[LG-GG-202204-01] ; Shanghai Municipal Science and Technology Major Project[2022YFC2703105] ; National Key R&D Program of China[2021M703341] ; National Key R&D Program of China[2023T160662] ; China Postdoctoral Science Foundation[2021423] ; Shanghai Post-doctoral Excellence Program |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:001220478200032 |
| 出版者 | NATURE PORTFOLIO |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/311243]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Cai, Hongmin; Xie, Xin; Xu, H. Eric |
| 作者单位 | 1.Inst Drug Discovery, Bohai Rim Adv Res, Shandong Lab Yantai Drug Discovery, Yantai, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 3.Univ Chinese Acad Sci, Sch Pharmaceut Sci & Technol, Hangzhou Inst Adv Study, Hangzhou, Peoples R China 4.Lingang Lab, Shanghai, Peoples R China 5.Univ Chinese Acad Sci, Beijing, Peoples R China 6.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Cai, Hongmin,Guo, Shimeng,Xu, Youwei,et al. Cryo-EM structures of adenosine receptor A3AR bound to selective agonists[J]. NATURE COMMUNICATIONS,2024,15(1):10. |
| APA | Cai, Hongmin.,Guo, Shimeng.,Xu, Youwei.,Sun, Jun.,Li, Junrui.,...&Xu, H. Eric.(2024).Cryo-EM structures of adenosine receptor A3AR bound to selective agonists.NATURE COMMUNICATIONS,15(1),10. |
| MLA | Cai, Hongmin,et al."Cryo-EM structures of adenosine receptor A3AR bound to selective agonists".NATURE COMMUNICATIONS 15.1(2024):10. |
入库方式： OAI收割
来源：上海药物研究所
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