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Membrane biology visualized in nanometer-sized discs formed by styrene maleic acid polymers

机译:在由苯乙烯马来酸聚合物形成的纳米大小的圆盘中可视化的膜生物学

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Abstract Discovering how membrane proteins recognize signals and passage molecules remains challenging. Life depends on compartmentalizing these processes into dynamic lipid bilayers that are technically difficult to work with. Several polymers have proven adept at separating the responsible machines intact for detailed analysis of their structures and interactions. Styrene maleic acid (SMA) co-polymers efficiently solubilize membranes into native nanodiscs and, unlike amphipols and membrane scaffold proteins, require no potentially destabilizing detergents. Here we review progress with the SMA lipid particle (SMALP) system and its impacts including three dimensional structures and biochemical functions of peripheral and transmembrane proteins. Polymers systems are emerging to tackle the remaining challenges for wider use and future applications including in membrane proteomics, structural biology of transient or unstable states, and discovery of ligand and drug-like molecules specific for native lipid-bound states. Graphical abstract Display Omitted Highlights ? Membrane protein complexes can be solubilized directly into native nanodiscs using styrene maleic acid polymers ? Structures of assemblies of multiple lipid and protein species purified together with SMA can be determined ? The interactions and specificities of polymer, lipid, protein and ligand molecules within these dynamic discs are being elucidated ? Optimized SMA polymers are expanding the range of conditions, affinity tags and visualization systems available
机译:摘要发现膜蛋白是如何识别信号和通道分子的仍然具有挑战性。生命取决于将这些过程的划分过程化为动态脂质双层,在技术上难以使用。在将负责机器完整分离的情况下,几种聚合物已被证明是为了详细分析它们的结构和相互作用。苯乙烯马来酸(SMA)共聚物有效地将膜溶解成天然纳米粥样族,并且与两酚和膜支架蛋白不同,不需要潜在的破坏性洗涤剂。在这里,我们审查了SMA脂质颗粒(Smalp)系统的进展及其冲击,包括外周和跨膜蛋白的三维结构和生物化学功能。聚合物系统正在涌现,以解决更广泛使用和未来应用的剩余挑战,包括膜蛋白质组学,瞬态或不稳定状态的结构生物学,以及对本地脂质结合态的粘合剂和药物状分子的发现。图形抽象显示省略了亮点?膜蛋白复合物可以使用苯乙烯马来酸聚合物直接溶解到天然纳米芯片中?可以确定与SMA一起纯化的多种脂质和蛋白质物种的组件的结构?在这些动态盘内的聚合物,脂质,蛋白质和配体分子的相互作用和特异性被阐明?优化的SMA聚合物正在扩展条件范围,亲和标签和可视化系统

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