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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
Mechanisms of chemokine recognition and receptor activation of chemokine receptor CCR7

文献类型：期刊论文

作者Cao, Yinglong6; Zhang, Chao5; Yuan, Qingning3; Zhao, Fenghui4,6; Liu, Qiufeng2; Wu, Kai1; Hu, Wen1; He, Jin1; Li, Hongchun6; Xu, H. Eric1,7
刊名CELL REPORTS
出版日期2025-11-25
卷号44期号:11页码:16
ISSN号2639-1856
DOI10.1016/j.celrep.2025.116582
英文摘要The chemokine receptor C-C chemokine receptor (CCR7) is essential for immune cell trafficking, cancer metastasis, and autoimmune diseases, making it a significant therapeutic target. This study presents cryo-electron microscopy (cryo-EM) structures of CCR7-Gi complexes bound to CCL19 and CCL21, revealing detailed interactions between the receptor, the two chemokines, and the G alpha i protein. Key N-terminal residues and a conserved aromatic patch in the orthosteric pocket are crucial for receptor activation by both ligands, with CCL19 also establishing additional polar interactions that are critical for this process. Mutagenesis studies demonstrate that mutations in these residues result in variable effects on ligandinduced activation, emphasizing the distinct interaction modes of CCL19 and CCL21 with CCR7. Notably, we identify an interesting activation mechanism for CCR7, in which the conventional toggle switch residue W 6.48 is replaced by Q 6.48 , leading to distinctive conformational changes upon ligand binding. These insights enhance our understanding of G-protein-coupled receptor (GPCR) signaling diversity and lay the groundwork for future therapeutic interventions targeting CCR7.
WOS关键词STRUCTURAL BASIS ; MIGRATION ; LIGAND ; MODEL ; METASTASIS ; EXPRESSION ; IMMUNITY ; MEDULLA ; CELLS ; ELC
资助项目National Natural Science Foundation of China[82373881] ; National Natural Science Foundation of China[32130022] ; National Natural Science Foundation of China[82121005] ; National Natural Science Foundation of China[82273985] ; National Natural Science Foundation of China[82473981] ; Young Elite Scientists Sponsorship Program by CAST[2022QNRC001] ; Shanghai Sailing Program[23YF1456800] ; Shanghai Sailing Program[22YF1457200] ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Lingang Laboratory[LG-8888] ; Lingang Laboratory[LG-GG-202204-01] ; CAS Strategic Priority Research Program[XDB37030103] ; CAS Strategic Priority Research Program[XDB1060402] ; Shanghai Municipal Science and Technology Major Project[2019SHZDZX02] ; National Key R&D Program of China[2022YFC2703105] ; National Key R&D Program of China[2023YFA1800804] ; National Research Center for Translational Medicine at Shanghai[NRCTM (SH) -2023-09]
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:001621945300001
出版者CELL PRESS
源URL[http://119.78.100.183/handle/2S10ELR8/322049]  
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Xu, H. Eric; Yang, Dehua; Duan, Jia
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
2.Shanghai Allist Pharmaceut Co Ltd, Shanghai, Peoples R China
3.Nanjing Univ Chinese Med, Coll Pharm, Nanjing 210023, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai 201203, Peoples R China
5.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China
6.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China
7.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
推荐引用方式
GB/T 7714		 Cao, Yinglong,Zhang, Chao,Yuan, Qingning,et al. Mechanisms of chemokine recognition and receptor activation of chemokine receptor CCR7[J]. CELL REPORTS,2025,44(11):16.
APA Cao, Yinglong.,Zhang, Chao.,Yuan, Qingning.,Zhao, Fenghui.,Liu, Qiufeng.,...&Duan, Jia.(2025).Mechanisms of chemokine recognition and receptor activation of chemokine receptor CCR7.CELL REPORTS,44(11),16.
MLA Cao, Yinglong,et al."Mechanisms of chemokine recognition and receptor activation of chemokine receptor CCR7".CELL REPORTS 44.11(2025):16.

入库方式： OAI收割

来源：上海药物研究所

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