Structural Basis for Chemokine Recognition and Receptor Activation of Chemokine Receptor CCR5

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Jul 7

PMID 34230484

Citations 38

Authors

Hui Zhang

Kun Chen

Qiuxiang Tan

Qiang Shao

Shuo Han

Chenhui Zhang

Cuiying Yi

Xiaojing Chu

Ya Zhu

Yechun Xu

Qiang Zhao

Beili Wu

Affiliations

Soon will be listed here.

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 G 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.

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