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

Hui Zhang, Kun Chen, Qiuxiang Tan, Qiang Shao, Shuo Han, Chenhui Zhang, Cuiying Yi, Xiaojing Chu, Ya Zhu (), Yechun Xu (), Qiang Zhao () and Beili Wu ()
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Hui Zhang: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Kun Chen: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Qiuxiang Tan: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Qiang Shao: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Shuo Han: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Chenhui Zhang: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Cuiying Yi: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Xiaojing Chu: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Ya Zhu: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Yechun Xu: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Qiang Zhao: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Beili Wu: Shanghai Institute of Materia Medica, Chinese Academy of Sciences

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract 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 Gi1 protein-coupled CCR5 in a ligand-free state and in complex with the chemokine MIP-1α or RANTES, as well as the crystal structure of MIP-1α-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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24438-5

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DOI: 10.1038/s41467-021-24438-5

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