Membrane Biochemistry and Biophysics, Bijvoet Center for Biomolecular Research, Institute of Biomembranes, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, and Bijvoet Center for Biomolecular Research, Utrecht University, 3584 CH Utrecht, The Netherlands.
Biomacromolecules. 2022 Mar 14;23(3):743-759. doi: 10.1021/acs.biomac.1c01166. Epub 2022 Jan 7.
Amphipathic copolymers such as poly(styrene-maleic acid) (SMA) are promising tools for the facile extraction of membrane proteins (MPs) into native nanodiscs. Here, we designed and synthesized a library of well-defined alternating copolymers of SMA analogues in order to elucidate polymer properties that are important for MP solubilization and stability. MP extraction efficiency was determined using KcsA from membranes, and general solubilization efficiency was investigated via turbidimetry experiments on membranes of , yeast mitochondria, and synthetic lipids. Remarkably, halogenation of SMA copolymers dramatically improved solubilization efficiency in all systems, while substituents on the copolymer backbone improved resistance to Ca. Relevant polymer properties were found to include hydrophobic balance, size and positioning of substituents, rigidity, and electronic effects. The library thus contributes to the rational design of copolymers for the study of MPs.
两亲性嵌段共聚物，如聚（苯乙烯-马来酸）（SMA），是将膜蛋白（MPs）轻易提取到天然纳米盘的有前途的工具。在这里，我们设计并合成了一系列具有明确结构的 SMA 类似物交替嵌段共聚物，以阐明对 MP 溶解和稳定性很重要的聚合物性质。使用来自 膜的 KcsA 来确定 MP 提取效率，并且通过浊度计实验在 酵母线粒体膜和合成脂质上研究了一般的溶解效率。值得注意的是，SMA 共聚物的卤化极大地提高了所有系统中的溶解效率，而共聚物主链上的取代基则提高了对 Ca 的抗性。发现相关的聚合物性质包括疏水性平衡、取代基的大小和位置、刚性和电子效应。因此，该文库有助于合理设计用于研究 MPs 的共聚物。
