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Structural insights into the activation and inhibition of CXC chemokine receptor 3

Nat Struct Mol Biol. 2024-01; 
Haizhan Jiao, Bin Pang, Aijun Liu, Qiang Chen, Qi Pan, Xiankun Wang, Yunong Xu, Ying-Chih Chiang, Ruobing Ren, Hongli Hu
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Proteins, Expression, Isolation and Analysis … Then the supernatant was collected and incubated with anti-DYKDDDDK G1 affinity resin (Genscript) for 1.5 h at 4 C. The resin was washed in buffer 20 mM HEPES-Na, pH 7.5, 100 … Get A Quote

摘要

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, accommodatin... More

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