Premium
Structural insights into the activation of chemokine receptor CXCR2
Author(s) -
Liu Kaiwen,
Shen Ling,
Wu Meng,
Liu ZhiJie,
Hua Tian
Publication year - 2022
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15865
Subject(s) - cxc chemokine receptors , allosteric regulation , chemokine receptor , chemistry , microbiology and biotechnology , g protein coupled receptor , chemokine , receptor , biology , biochemistry
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.