8KFX

Gi bound CCR8 complex with nonpeptide agonist LMD-009

8KFX の概要

• エントリーDOI: 10.2210/pdb8kfx/pdb
• EMDBエントリー: 37207
• 分子名称: Guanine 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)
• 機能のキーワード: gpcr gi agonist, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 185465.23

構造登録者

Jiang, S.,Lin, X.,Wu, L.J.,Xu, F. (登録日: 2023-08-16, 公開日: 2024-02-07, 最終更新日: 2025-07-23)

主引用文献

Jiang, 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

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

実験手法

ELECTRON MICROSCOPY (2.96 Å)