Modular detergents tailor the purification and structural analysis of membrane proteins including G-protein coupled receptors
Modular detergents tailor the purification and structural analysis of membrane proteins including G-protein coupled receptors
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DOI：
10.1038/s41467-020-14424-8
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发表时间：
2020-01-28
影响因子：
16.6
通讯作者：
Pagel, Kevin
中科院分区：
文献类型：
--
作者：
Urner, Leonhard H.;Liko, Idlir;Pagel, Kevin
去污剂能够纯化膜蛋白，是结构生物学中不可或缺的试剂。尽管上个世纪已经开发出多种去污剂，但确定指导方针以允许针对膜蛋白研究中的个别应用对去污剂进行微调仍然是一项挑战。为了应对这一挑战，我们在此介绍低聚甘油洗涤剂 (OGD) 系列。天然质谱 (MS) 表明，模块化 OGD 架构能够控制蛋白质纯化并在纯化过程中保留与天然膜脂的相互作用。除了广泛的细菌膜蛋白之外，OGD 还可以纯化和分析功能性 G 蛋白偶联受体 (GPCR)。此外，考虑到这些去垢剂的模块化设计，我们预计可以针对结构生物学中的特定应用对其特性进行微调。从更广泛的角度来看，这代表了膜蛋白及其与脂质相互作用的研究的重大进展。
Detergents enable the purification of membrane proteins and are indispensable reagents in structural biology. Even though a large variety of detergents have been developed in the last century, the challenge remains to identify guidelines that allow fine-tuning of detergents for individual applications in membrane protein research. Addressing this challenge, here we introduce the family of oligoglycerol detergents (OGDs). Native mass spectrometry (MS) reveals that the modular OGD architecture offers the ability to control protein purification and to preserve interactions with native membrane lipids during purification. In addition to a broad range of bacterial membrane proteins, OGDs also enable the purification and analysis of a functional G-protein coupled receptor (GPCR). Moreover, given the modular design of these detergents, we anticipate fine-tuning of their properties for specific applications in structural biology. Seen from a broader perspective, this represents a significant advance for the investigation of membrane proteins and their interactions with lipids.