8XML
Cryo-EM structure of the Apo CCR8-Gi complex
Summary for 8XML
| Entry DOI | 10.2210/pdb8xml/pdb |
| EMDB information | 38481 |
| Descriptor | Soluble cytochrome b562,C-C chemokine receptor type 8, Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (5 entities in total) |
| Functional Keywords | cryo-em, ccr8, gpcr, structural protein |
| Biological source | Escherichia coli More |
| Total number of polymer chains | 5 |
| Total formula weight | 167079.53 |
| Authors | Peng, Q.,Jiang, H.H.,Cheng, X.Y.,Li, J.,Zhang, J. (deposition date: 2023-12-27, release date: 2025-01-01, Last modification date: 2026-01-14) |
| Primary citation | Peng, Q.,Jiang, H.,Cheng, X.,Wang, N.,Zhou, S.,Zhang, Y.,Yang, T.,Chen, Y.,Zhang, W.,Lv, S.,Nan, W.,Wang, J.,Fan, G.H.,Li, J.,Zhang, J. Cryo-EM Structure and Biochemical Analysis of the Human Chemokine Receptor CCR8. Biochemistry, 63:1892-1900, 2024 Cited by PubMed Abstract: The C-C motif chemokine receptor 8 (CCR8) is a class A G-protein-coupled receptor that has emerged as a promising therapeutic target in cancer and autoimmune diseases. In the present study, we solved the cryo-electron microscopy (cryo-EM) structure of the human CCR8-G complex in the absence of a ligand at 2.58 Å. Structural analysis and comparison revealed that our apo CCR8 structure undergoes some conformational changes and is similar to that in the CCL1-CCR8 complex structure, indicating an active state. In addition, the key residues of CCR8 involved in the recognition of LMD-009, a potent nonpeptide agonist, were investigated by mutating CCR8 and testing the calcium flux induced by LMD-009-CCR8 interaction. Three mutants of CCR8, Y113A, Y172A, and E286A, showed a dramatically decreased ability in mediating calcium mobilization, indicating their key interaction with LMD-009 and key roles in activation. These structural and biochemical analyses enrich molecular insights into the agonism and activation of CCR8 and will facilitate CCR8-targeted therapy. PubMed: 38985857DOI: 10.1021/acs.biochem.4c00121 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.58 Å) |
Structure validation
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