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QTY code designed thermostable and water-soluble chimeric chemokine receptors with tunable ligand affinity

Proc Natl Acad Sci U S A. 2019-11-01; 
Rui Qing, Qiuyi Han, Michael Skuhersky, Haeyoon Chung, Myriam Badr, Thomas Schubert, Shuguang Zhang
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摘要

Chemokine receptors are of great interest as they play a critical role in many immunological and pathological processes. The ability to study chemokine receptors in aqueous solution without detergent would be significant because natural receptors require detergents to become soluble. We previously reported using the QTY code to design detergent-free chemokine receptors. We here report the design of 2 detergent-free chimeric chemokine receptors that were experimentally unattainable in detergent solution. We designed chimeric receptors by switching the N terminus and 3 extracellular (EC) loops between different receptors. Specifically, we replaced the N terminus and 3 EC loops of CCR5 with the N terminus and 3 EC... More

关键词

CCR5, CXCR4, GPCR, chimera receptors, membrane protein design