Luo Weiling, Yang Meifang, Zhao Yitian, Wang Huixia, Yang Xiaodi, Zhang Wei, Zhao Fei, Zhao Suwen, Tao Houchao
Shanghai Frontiers Science Center of TCM Chemical Biology, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 201203, Shanghai, P. R. China.
iHuman Institute, ShanghaiTech University, 201210, Shanghai, P. R. China.
Chemistry. 2022 Dec 9;28(69):e202202242. doi: 10.1002/chem.202202242. Epub 2022 Oct 17.
It is a pressing need, but still challenging to explore the structure and function of membrane proteins (MPs). One of the main obstacles is the limited availability of matched detergents for the handling of specific MPs. We describe herein the design of new detergents by incorporation of a transition linker between the hydrophilic head and the hydrophobic tail. This design allows a gradual change of hydrophobicity between the outside and inside of micelles, in contrast to the abrupt switch in conventional detergents. Notably, many of these detergents assembled into micelles in while retaining low critical micelle concentrations. Meanwhile, thermal stabilizing evaluation identified superior detergents for representative MPs, including G protein-coupled receptors and a transporter protein. Among them, further improved the NMR study of MPs. We anticipate these that results will encourage future detergent expansion through new remodeling on the traditional detergent scaffold.
探索膜蛋白(MPs)的结构和功能是一项紧迫需求,但仍具有挑战性。主要障碍之一是用于处理特定MPs的匹配去污剂的可用性有限。我们在此描述了通过在亲水头部和疏水尾部之间引入过渡连接体来设计新型去污剂。与传统去污剂的突然转变不同,这种设计允许胶束内外的疏水性逐渐变化。值得注意的是,这些去污剂中的许多在保持低临界胶束浓度的同时组装成胶束。同时,热稳定性评估确定了用于代表性MPs(包括G蛋白偶联受体和转运蛋白)的优质去污剂。其中,进一步改善了MPs的核磁共振研究。我们预计这些结果将通过对传统去污剂支架进行新的重塑来鼓励未来去污剂的扩展。