Biophysics Program, The University of Michigan, Ann Arbor, MI 48109-1055, USA; Department of Chemistry, The University of Michigan, Ann Arbor, MI 48109-1055, USA.
Department of Chemistry, The University of Michigan, Ann Arbor, MI 48109-1055, USA.
Chem Phys Lipids. 2019 Mar;219:45-49. doi: 10.1016/j.chemphyslip.2019.01.010. Epub 2019 Jan 29.
There is considerable interest in the development of membrane mimetics to study the structure, dynamics and function of membrane proteins. Polymer nanodiscs have been useful as a membrane mimetic by not only providing a native-like membrane environment, but also have the ability to extract the desired membrane protein directly from the cell membrane. In spite of such great potential, polymer nanodiscs have their disadvantages including lack of size control and instability at low pH and with divalent metals. In this review, we discuss how these limitations have been overcome by simple modifications of synthetic polymers commonly used to form nanodiscs. Recently, size control has been achieved using an ethanolamine functionalization of a low molecular weight polymer. This size control enabled the use of polymer-based lipid-nanodiscs in solution NMR and macro-nanodiscs in solid-state NMR applications. The introduction of quaternary ammonium functional groups has been shown to improve the stability in the presence of low pH and divalent metal ions, forming highly monodispersed nanodiscs. The polymer charge has been shown to play a significant role on the reconstitution of membrane proteins due to the high charge density on the nanodisc's belt. These recent developments have expanded the applications of polymer nanodiscs to study the membrane proteins using wide variety of techniques including NMR, Cryo-EM and other biophysical techniques.
人们对开发膜模拟物来研究膜蛋白的结构、动力学和功能非常感兴趣。聚合物纳米盘不仅提供了类似天然的膜环境，而且能够直接从细胞膜中提取所需的膜蛋白，因此作为膜模拟物非常有用。尽管具有如此巨大的潜力，但聚合物纳米盘也存在一些缺点，例如缺乏尺寸控制和在低 pH 值和二价金属存在下的不稳定性。在这篇综述中，我们讨论了如何通过对常用于形成纳米盘的合成聚合物进行简单的修饰来克服这些限制。最近，通过对低分子量聚合物进行乙醇胺官能化实现了尺寸控制。这种尺寸控制使得聚合物基脂质纳米盘能够在溶液 NMR 中使用，而在固态 NMR 应用中能够使用大尺寸纳米盘。引入季铵官能团已被证明可以提高在低 pH 值和二价金属离子存在下的稳定性，形成高度单分散的纳米盘。由于纳米盘带上的高电荷密度，聚合物的电荷已被证明对膜蛋白的重组成分起着重要作用。这些最新的发展扩展了聚合物纳米盘的应用范围，使其能够使用各种技术，包括 NMR、冷冻电镜和其他生物物理技术，来研究膜蛋白。
