Structural basis of CXC chemokine receptor 2 activation and signalling

doi:10.1038/s41586-020-2492-5

	Structural basis of CXC chemokine receptor 2 activation and signalling
	Liu, Kaiwen1,2,3,4 ; Wu, Lijie1 ; Yuan, Shuguang 5; Wu, Meng1,2,3 ; Xu, Yueming1 ; Sun, Qianqian1 ; Li, Shu 5; Zhao, Suwen1,2 ; Hua, Tian1 ; Liu, Zhi-Jie1,2
	2020-09-03
发表期刊	NATURE (IF:50.5[JCR-2023],54.4[5-Year])
ISSN	0028-0836
EISSN	1476-4687
发表状态	已发表
DOI	10.1038/s41586-020-2492-5
摘要	Chemokines and their receptors mediate cell migration, which influences multiple fundamental biological processes and disease conditions such as inflammation and cancer(1). Although ample effort has been invested into the structural investigation of the chemokine receptors and receptor-chemokine recognition(2-4), less is known about endogenous chemokine-induced receptor activation and G-protein coupling. Here we present the cryo-electron microscopy structures of interleukin-8 (IL-8, also known as CXCL8)-activated human CXC chemokine receptor 2 (CXCR2) in complex with G(i) protein, along with a crystal structure of CXCR2 bound to a designed allosteric antagonist. Our results reveal a unique shallow mode of binding between CXCL8 and CXCR2, and also show the interactions between CXCR2 and G(i) protein. Further structural analysis of the inactive and active states of CXCR2 reveals a distinct activation process and the competitive small-molecule antagonism of chemokine receptors. In addition, our results provide insights into how a G-protein-coupled receptor is activated by an endogenous protein molecule, which will assist in the rational development of therapeutics that target the chemokine system for better pharmacological profiles.
收录类别	SCI ; SCIE
语种	英语
资助项目	National Natural Science Foundation of China[31930060][91953202] ; CAS Strategic Priority Research Program[XDB37030104] ; National Key Research and Development Program of China[2018YFA0507000] ; Shenzhen Institutes of Advanced Technology, CAS grant[1105150101] ; Interdisciplinary Centre for Mathematical and Computational Modelling in Warsaw[GB71-3][GB70-3]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000563193600001
出版者	NATURE PUBLISHING GROUP
WOS关键词	CRYO-EM STRUCTURE ; CRYSTAL-STRUCTURE ; MEMBRANE-PROTEINS ; TERMINAL DOMAIN ; INTERLEUKIN-8 ; BINDING ; RECOGNITION ; LIGAND ; ELECTROSTATICS ; MODULATION
原始文献类型	Article ; Early Access
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/123087
专题	iHuman研究所_PI研究组_华甜组生命科学与技术学院 iHuman研究所_公共科研平台_生命科学电镜平台 iHuman研究所_公共科研平台_IT平台 iHuman研究所_PI研究组_刘志杰组 iHuman研究所_PI研究组_赵素文组 iHuman研究所_科学装置(X)_膜蛋白同步辐射线站
通讯作者	Hua, Tian; Liu, Zhi-Jie
作者单位	1.ShanghaiTech Univ, iHuman Inst, Shanghai, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 3.Univ Chinese Acad Sci, Beijing, Peoples R China 4.Chinese Acad Sci, Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, Shanghai, Peoples R China 5.Chinese Acad Sci, Res Ctr Comp Aided Drug Discovery, Shenzhen Inst Adv Technol, Shenzhen, Peoples R China
第一作者单位	iHuman研究所; 生命科学与技术学院
通讯作者单位	iHuman研究所; 生命科学与技术学院
第一作者的第一单位	iHuman研究所
推荐引用方式 GB/T 7714	Liu, Kaiwen,Wu, Lijie,Yuan, Shuguang,et al. Structural basis of CXC chemokine receptor 2 activation and signalling[J]. NATURE,2020.
APA	Liu, Kaiwen.,Wu, Lijie.,Yuan, Shuguang.,Wu, Meng.,Xu, Yueming.,...&Liu, Zhi-Jie.(2020).Structural basis of CXC chemokine receptor 2 activation and signalling.NATURE.
MLA	Liu, Kaiwen,et al."Structural basis of CXC chemokine receptor 2 activation and signalling".NATURE (2020).