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Structural basis for chemokine recognition and receptor activation of chemokine receptor CCR5

文献类型：期刊论文

作者Zhang, Hui1,2,3; Chen, Kun1,2,3; Tan, Qiuxiang1; Shao, Qiang1; Han, Shuo3; Zhang, Chenhui1,2,3; Yi, Cuiying3; Chu, Xiaojing1; Zhu, Ya3; Xu, Yechun1,2,4
刊名NATURE COMMUNICATIONS
出版日期2021-07-06
卷号12期号:1页码:12
ISSN号2041-1723
DOI10.1038/s41467-021-24438-5
通讯作者Zhu, Ya(zhuya2@simm.ac.cn) ; Xu, Yechun(ycxu@simm.ac.cn) ; Zhao, Qiang(zhaoq@simm.ac.cn) ; Wu, Beili(beiliwu@simm.ac.cn)
英文摘要The chemokine receptor CCR5 plays a vital role in immune surveillance and inflammation. However, molecular details that govern its endogenous chemokine recognition and receptor activation remain elusive. Here we report three cryo-electron microscopy structures of G(i1) protein-coupled CCR5 in a ligand-free state and in complex with the chemokine MIP-1 alpha or RANTES, as well as the crystal structure of MIP-1 alpha -bound CCR5. These structures reveal distinct binding modes of the two chemokines and a specific accommodate pattern of the chemokine for the distal N terminus of CCR5. Together with functional data, the structures demonstrate that chemokine-induced rearrangement of toggle switch and plasticity of the receptor extracellular region are critical for receptor activation, while a conserved tryptophan residue in helix II acts as a trigger of receptor constitutive activation. The chemokine receptor CCR5 plays multiple roles in the immune system. Here, structures of G(i1) protein-coupled CCR5 with or without a chemokine bound and of the CCR5- chemokine MIP-1 alpha complex offer insight into the distinct binding modes of the ligands and into the mechanism of CCR5 activation.
WOS关键词ACCELERATED MOLECULAR-DYNAMICS ; TYROSINE SULFATION ; TRANSMEMBRANE HELIX ; TXP MOTIF ; PROTEIN ; BINDING ; MODULATION ; SOFTWARE ; ACCURACY ; SYSTEM
资助项目National Science Foundation of China[31730027] ; National Science Foundation of China[31825010] ; National Science Foundation of China[31800618] ; National Key R&D Programs of China[2018YFA0507000] ; National Key R&D Programs of China[2016YFA0502301] ; CAS Strategic Priority Research Program[XDB37030100] ; China Postdoctoral Science Foundation[Y91204R081] ; China Postdoctoral Science Foundation[Y91205R081]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000672715100002
出版者NATURE RESEARCH
源URL[http://119.78.100.183/handle/2S10ELR8/296943]  
专题新药研究国家重点实验室
通讯作者Zhu, Ya; Xu, Yechun; Zhao, Qiang; Wu, Beili
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai, Peoples R China
2.Univ Chinese Acad Sci, Beijing, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China
4.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou, Peoples R China
5.Chinese Acad Sci, Zhongshan Branch, Inst Drug Discovery & Dev, Zhongshan, Peoples R China
6.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Zhang, Hui,Chen, Kun,Tan, Qiuxiang,et al. Structural basis for chemokine recognition and receptor activation of chemokine receptor CCR5[J]. NATURE COMMUNICATIONS,2021,12(1):12.
APA Zhang, Hui.,Chen, Kun.,Tan, Qiuxiang.,Shao, Qiang.,Han, Shuo.,...&Wu, Beili.(2021).Structural basis for chemokine recognition and receptor activation of chemokine receptor CCR5.NATURE COMMUNICATIONS,12(1),12.
MLA Zhang, Hui,et al."Structural basis for chemokine recognition and receptor activation of chemokine receptor CCR5".NATURE COMMUNICATIONS 12.1(2021):12.

入库方式： OAI收割

来源：上海药物研究所

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