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Publication Abstract from PubMed

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-1alpha or RANTES, as well as the crystal structure of MIP-1alpha-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.

Structural basis for chemokine recognition and receptor activation of chemokine receptor CCR5.,Zhang H, Chen K, Tan Q, Shao Q, Han S, Zhang C, Yi C, Chu X, Zhu Y, Xu Y, Zhao Q, Wu B Nat Commun. 2021 Jul 6;12(1):4151. doi: 10.1038/s41467-021-24438-5. PMID:34230484^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.