Structural insights into the activation of chemokine receptor CXCR2

被引：12
作者：
Liu, Kaiwen [1 ]
Shen, Ling [1 ,2 ,3 ,4 ]
Wu, Meng [1 ]
Liu, Zhi-Jie [1 ,2 ]
Hua, Tian [1 ,2 ]
机构：
[1] ShanghaiTech Univ, Human 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, Shanghai Inst Biochem & Cell Biol, Ctr Excellence Mol Cell Sci, Shanghai, Peoples R China
来源：
FEBS JOURNAL | 2022年 / 289卷 / 02期
关键词：
activation; chemokine receptor; cryo-EM; CXCL8; CXCR2; INTERLEUKIN-8; PROTEIN; POTENT; RECOGNITION; CANCER; ANTAGONIST; MODULATION; NEUTROPHIL; DOCKING; GLIDE;
D O I：
10.1111/febs.15865
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The C-X-C motif chemokine CXCL8 (interleukin-8, IL-8) and its receptor chemokine receptor 2 (CXCR2) mediate neutrophil migration during cell development and inflammatory responses and thus are related to numerous inflammatory diseases and cancers. We have determined the cryo-electron microscopy structure of CXCL8 bound CXCR2 coupled to G(i) protein, as well as the crystal structure of inactive CXCR2 in complex with a designed allosteric antagonist. These results reveal the binding modes between CXCL8 and CXCR2, CXCR2 and G protein, and the detailed binding pattern of the allosteric antagonist, 00767013. Further structural analysis of the inactive- and active- states of CXCR2 reveals the unique shallow-pocket activation mechanism of C-X-C chemokine receptors and promotes our understanding on how a G protein-coupled receptor (GPCR) is activated by an endogenous protein molecule. In addition, the cholesterol molecule is observed in the activated CXCR2 structure, providing the structural basis of the potential allosteric modulation role of cholesterol in chemokine receptors.
引用
收藏
页码：386 / 393
页数：8
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