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

doi:10.1038/s41467-021-24438-5

	Structural basis for chemokine recognition and receptor activation of chemokine receptor CCR5
	Zhang, Hui 1,2,3; Chen, Kun 1,2,3; Tan, Qiuxiang 1; Shao, Qiang 1; Han, Shuo 2; Zhang, Chenhui 1,2,3; Yi, Cuiying 2; Chu, Xiaojing 1; Zhu, Ya 2; Xu, Yechun 1,3,4; Zhao, Qiang 2,3,4,5; Wu, Beili1,3,4,6
	2021-07-06
发表期刊	NATURE COMMUNICATIONS (IF:14.7[JCR-2023],16.1[5-Year])
ISSN	2041-1723
卷号	12 期号:1
DOI	10.1038/s41467-021-24438-5
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.
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收录类别	SCIE
语种	英语
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000672715100002
出版者	NATURE RESEARCH
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/127724
专题	生命科学与技术学院_特聘教授组_吴蓓丽组
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.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China; 3.Univ Chinese Acad Sci, Beijing, 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
通讯作者单位	生命科学与技术学院
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).
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).
MLA	Zhang, Hui,et al."Structural basis for chemokine recognition and receptor activation of chemokine receptor CCR5".NATURE COMMUNICATIONS 12.1(2021).