Detergent-free systems for structural studies of membrane proteins.
Detergent-free systems for structural studies of membrane proteins.
复制标题
用于膜蛋白结构研究的无洗涤剂系统。
DOI：
10.1042/bst20201080
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发表时间：
2021-06-30
影响因子：
3.9
通讯作者：
Guo Y
中科院分区：
文献类型：
--
作者：
Guo Y
膜蛋白在生物体中起着至关重要的作用，是目前大多数处方药物的靶点。膜蛋白结构生物学旨在提供准确的结构信息，以了解其作用机制。在过去的几十年里，膜蛋白结构生物学的进展主要依赖于基于去污剂的方法。然而，基于去污剂的方法具有显著的缺点，因为去污剂通常会破坏天然蛋白质-脂质相互作用，而天然蛋白质-脂质相互作用通常对于维持膜蛋白的天然结构和功能至关重要。无洗涤剂的方法最近已经出现作为具有很大前景的替代品，例如用于在其天然细胞膜脂质环境中膜蛋白的高分辨率结构测定。这篇小评论批判性地研究了无洗涤剂方法的现状，通过对五组使用无洗涤剂和基于洗涤剂的方法确定的膜蛋白结构的比较分析。该分析表明，目前的无洗涤剂系统，如苯乙烯-马来酸脂质颗粒（SMALP），二异丁基马来酸脂质颗粒（DIBMALP），和环烷改性的两亲聚合物（CyclAPol）技术是不是更好的比基于洗涤剂的方法在跨膜结构域上的天然细胞膜脂质的维护和高分辨率的结构测定。然而，另一种无洗涤剂技术，天然细胞膜纳米颗粒（NCMN）系统，证明了天然细胞膜脂质与所研究的膜蛋白的改善的维护，并产生适合于高分辨率结构分析的颗粒。新的膜活性聚合物的持续开发及其优化将促进这些新的无洗涤剂体系的成熟。
Membrane proteins play vital roles in living organisms, serving as targets for most currently prescribed drugs. Membrane protein structural biology aims to provide accurate structural information to understand their mechanisms of action. The advance of membrane protein structural biology has primarily relied on detergent-based methods over the past several decades. However, detergent-based approaches have significant drawbacks because detergents often damage the native protein–lipid interactions, which are often crucial for maintaining the natural structure and function of membrane proteins. Detergent-free methods recently have emerged as alternatives with a great promise, e.g. for high-resolution structure determinations of membrane proteins in their native cell membrane lipid environments. This minireview critically examines the current status of detergent-free methods by a comparative analysis of five groups of membrane protein structures determined using detergent-free and detergent-based methods. This analysis reveals that current detergent-free systems, such as the styrene-maleic acid lipid particles (SMALP), the diisobutyl maleic acid lipid particles (DIBMALP), and the cycloalkane-modified amphiphile polymer (CyclAPol) technologies are not better than detergent-based approaches in terms of maintenance of native cell membrane lipids on the transmembrane domain and high-resolution structure determination. However, another detergent-free technology, the native cell membrane nanoparticles (NCMN) system, demonstrated improved maintenance of native cell membrane lipids with the studied membrane proteins, and produced particles that were suitable for high-resolution structural analysis. The ongoing development of new membrane-active polymers and their optimization will facilitate the maturation of these new detergent-free systems.