| Title |
Structural basis for chemokine recognition and receptor activation of chemokine receptor CCR5 |
| Description |
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 1a or RANTES, as well as the crystal structure of MIP 1a 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. |
| Organism |
Homo sapiens |
| Data Type |
Protein 3D Structure Data |
| Data Accessibility |
Controlled-access |
| BioProject |
PRJCA016824 |
| Release Date |
2024-12-31 |
| Submitter |
wenru zhang (wrzhang@simm.ac.cn) |
| Organization |
Shanghai nstitute of Material Medica |
| Submission Date |
2023-05-08 |