8HNL

CXCR3-DNGi complex activated by PS372424

8HNL の概要

• エントリーDOI: 10.2210/pdb8hnl/pdb
• EMDBエントリー: 34915
• 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, ... (7 entities in total)
• 機能のキーワード: g protein coupled receptor, chemokine receptor, cxcr3, ps372424, complex, 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: 192377.05

構造登録者

Jiao, H.Z.,Hu, H.L. (登録日: 2022-12-08, 公開日: 2023-11-29, 最終更新日: 2024-10-16)

主引用文献

Jiao, H.,Pang, B.,Liu, A.,Chen, Q.,Pan, Q.,Wang, X.,Xu, Y.,Chiang, Y.C.,Ren, R.,Hu, H.
Structural insights into the activation and inhibition of CXC chemokine receptor 3.
Nat.Struct.Mol.Biol., 31:610-620, 2024

PubMed Abstract: The chemotaxis of CD4 type 1 helper cells and CD8 cytotoxic lymphocytes, guided by interferon-inducible CXC chemokine 9-11 (CXCL9-11) and CXC chemokine receptor 3 (CXCR3), plays a critical role in type 1 immunity. Here we determined the structures of human CXCR3-DNG complexes activated by chemokine CXCL11, peptidomimetic agonist PS372424 and biaryl-type agonist VUF11222, and the structure of inactive CXCR3 bound to noncompetitive antagonist SCH546738. Structural analysis revealed that PS372424 shares a similar orthosteric binding pocket to the N terminus of CXCL11, while VUF11222 buries deeper and activates the receptor in a distinct manner. We showed an allosteric binding site between TM5 and TM6, accommodating SCH546738 in the inactive CXCR3. SCH546738 may restrain the receptor at an inactive state by preventing the repacking of TM5 and TM6. By revealing the binding patterns and the pharmacological properties of the four modulators, we present the activation mechanisms of CXCR3 and provide insights for future drug development.

PubMed: 38177682
DOI: 10.1038/s41594-023-01175-5

実験手法

ELECTRON MICROSCOPY (2.98 Å)