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-Structure paper
Title | Structural basis for chemokine recognition and receptor activation of chemokine receptor CCR5. |
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Journal, issue, pages | Nat Commun, Vol. 12, Issue 1, Page 4151, Year 2021 |
Publish date | Jul 6, 2021 |
![]() | Hui Zhang / Kun Chen / Qiuxiang Tan / Qiang Shao / Shuo Han / Chenhui Zhang / Cuiying Yi / Xiaojing Chu / Ya Zhu / Yechun Xu / Qiang Zhao / Beili Wu / ![]() |
PubMed 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 ...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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Methods | EM (single particle) / X-ray diffraction |
Resolution | 2.6 - 3.0 Å |
Structure data | EMDB-31422, PDB-7f1q: EMDB-31423, PDB-7f1r: EMDB-31424, PDB-7f1s: ![]() PDB-7f1t: |
Chemicals | ![]() ChemComp-ZN: |
Source |
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![]() | SIGNALING PROTEIN / G Protein-coupled receptor / Chemokine Receptor CCR5 / MIP-1a / RANTES / G protein |