Accessible Mannitol-Based Amphiphiles (MNAs) for Membrane Protein Solubilisation and Stabilisation
Accessible Mannitol-Based Amphiphiles (MNAs) for Membrane Protein Solubilisation and Stabilisation
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DOI：
10.1002/chem.201600533
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发表时间：
2016-05-17
影响因子：
4.3
通讯作者：
Chae, Pil Seok
中科院分区：
文献类型：
--
作者：
Hussain, Hazrat;Du, Yang;Chae, Pil Seok
整合膜蛋白是对所有细胞生命至关重要的两亲性分子。这些大分子的结构研究从天然膜中提取蛋白质开始，然后进行纯化和结晶。洗涤剂是这些过程的重要工具，但洗涤剂溶解的膜蛋白经常变性和聚集，导致结构和功能丧失。在这项研究中，制备了一类新型试剂，称为基于甘露醇的两亲物 (MNA)，并对其溶解和稳定膜蛋白的能力进行了表征。与正十二烷基-D-麦芽糖苷 (DDM) 和其他 MNA 相比，一些 MNA 增强了四种膜蛋白的稳定性，包括 G 蛋白偶联受体 (GPCR)、β(2) 肾上腺素能受体 (β(2)AR)。这些试剂对于 β(2)AR 的电子显微镜分析也优于 DDM。易于制备以及增强的膜蛋白稳定功效证明了这些试剂对于未来膜蛋白研究的价值。
Integral membrane proteins are amphipathic molecules crucial for all cellular life. The structural study of these macromolecules starts with protein extraction from the native membranes, followed by purification and crystallisation. Detergents are essential tools for these processes, but detergent-solubilised membrane proteins often denature and aggregate, resulting in loss of both structure and function. In this study, a novel class of agents, designated mannitol-based amphiphiles (MNAs), were prepared and characterised for their ability to solubilise and stabilise membrane proteins. Some of MNAs conferred enhanced stability to four membrane proteins including a G protein-coupled receptor (GPCR), the beta(2) adrenergic receptor (beta(2)AR), compared to both n-dodecyl-D-maltoside (DDM) and the other MNAs. These agents were also better than DDM for electron microscopy analysis of the beta(2)AR. The ease of preparation together with the enhanced membrane protein stabilisation efficacy demonstrates the value of these agents for future membrane protein research.