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8KFY

Gi bound CCR8 complex with nonpeptide agonist ZK 756326

Summary for 8KFY
Entry DOI10.2210/pdb8kfy/pdb
EMDB information37208
DescriptorGuanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (6 entities in total)
Functional Keywordsgpcr, gi, agonist, signaling protein
Biological sourceHomo sapiens (human)
More
Total number of polymer chains5
Total formula weight185350.09
Authors
Jiang, S.,Lin, X.,Wu, L.J.,Xu, F. (deposition date: 2023-08-16, release date: 2024-02-07, Last modification date: 2024-11-13)
Primary citationJiang, S.,Lin, X.,Wu, L.,Wang, L.,Wu, Y.,Xu, Z.,Xu, F.
Unveiling the structural mechanisms of nonpeptide ligand recognition and activation in human chemokine receptor CCR8.
Sci Adv, 10:eadj7500-eadj7500, 2024
Cited by
PubMed Abstract: The human CC chemokine receptor 8 (CCR8) is an emerging therapeutic target for cancer immunotherapy and autoimmune diseases. Understanding the molecular recognition of CCR8, particularly with nonpeptide ligands, is valuable for drug development. Here, we report three cryo-electron microscopy structures of human CCR8 complexed with G trimers in the ligand-free state or activated by nonpeptide agonists LMD-009 and ZK 756326. A conserved YYE motif in the orthosteric binding pocket is shown to play a crucial role in the chemokine and nonpeptide ligand recognition. Structural and functional analyses indicate that the lack of conservation in Y114 and Y172 among the CC chemokine receptors could potentially contribute to the selectivity of the nonpeptide ligand binding to CCR8. These findings present the characterization of the molecular interaction between a nonpeptide agonist and a chemokine receptor, aiding the development of therapeutics targeting related diseases through a structure-based approach.
PubMed: 38306437
DOI: 10.1126/sciadv.adj7500
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3.06 Å)
Structure validation

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