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Review
. 2022 Jan;289(2):386-393.
doi: 10.1111/febs.15865. Epub 2021 Apr 21.

Structural insights into the activation of chemokine receptor CXCR2

Kaiwen Liu  1 , Ling Shen  1   2   3   4 , Meng Wu  1 , Zhi-Jie Liu  1   2 , Tian Hua  1   2
Affiliations
Free article
Review

Structural insights into the activation of chemokine receptor CXCR2

Kaiwen Liu et al. FEBS J. 2022 Jan.
Free article

Abstract

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 Gi 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.

Keywords: CXCL8; CXCR2; activation; chemokine receptor; cryo-EM.

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References

    1. Le Y, Zhou Y, Iribarren P & Wang J (2004) Chemokines and chemokine receptors: their manifold roles in homeostasis and disease. Cell Mol Immunol 1, 95-104.
    1. Gerber PA, Hippe A, Buhren BA, Muller A & Homey B (2009) Chemokines in tumor-associated angiogenesis. Biol Chem 390, 1213-1223.
    1. Rossi D & Zlotnik A (2000) The biology of chemokines and their receptors. Annu Rev Immunol 18, 217-242.
    1. Baggiolini M (1998) Chemokines and leukocyte traffic. Nature 392, 565-568.
    1. Clore GM, Appella E, Yamada M, Matsushima K & Gronenborn AM (1990) Three-dimensional structure of interleukin 8 in solution. Biochemistry 29, 1689-1696.

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