Polymer Nanodiscs as New Platforms for Membrane Proteins
Polymer Nanodiscs as New Platforms for Membrane Proteins
复制标题
聚合物纳米圆盘作为膜蛋白的新平台
DOI：
10.1016/j.bpj.2017.11.2524
复制
发表时间：
2018
影响因子：
3.4
通讯作者：
Liang, Hongjun
中科院分区：
文献类型：
--
作者：
Fiori, Mariana C.;Jiang, Yunjiang;Zheng, Wan;Anzaldua, Miguel;Borgnia, Mario J.;Altenberg, Guillermo A.;Liang, Hongjun
脂质纳米盘（LND）是由脂质双层膜贴片包裹在载脂蛋白A1衍生的膜支架蛋白（MSP）内组成的盘状纳米结构。LND在膜蛋白结构和功能的研究中发挥着越来越重要的作用。最近的发展是使用苯乙烯-马来酸（SMA）共聚物将MP溶解和重构成纳米盘。这些聚合物包裹的纳米盘（SMALP，SMA脂质颗粒）是在接近生理环境中研究MP而不使用洗涤剂的有前途的平台。然而，目前的SMA共聚物在缓冲液相容性和随之而来的各种应用的灵活性方面显示出严重的限制。此外，纳米盘作为MP支持平台或药物靶向和递送载体的开发受到脂质双层的流体和不稳定性质的破坏。在这里，我们引入新的方法来解决SMALP和LND的一些缺点，通过使用一组新的嵌段共聚物来代替MSP和另一组嵌段共聚物来代替脂质双层。我们的新型两性离子苯乙烯-马来酸衍生物共聚物（zSMAs）家族在低pH值或存在多价阳离子的情况下不会聚集（正如商业SMAs所做的那样），并且可用于溶解MP并生产受控尺寸的纳米盘。我们还介绍了聚合物纳米盘（PND），盘状的两亲性嵌段共聚物膜补丁封装在MSP。PND是新型的二维纳米膜，其保持LND的优点，同时解决其稳定性弱点。我们预计，嵌段共聚物膜更高的机械和化学稳定性及其适应的化学多功能性将为基于不同MP功能或涉及药物靶向和递送的应用开辟新的机会。
Lipid nanodiscs (LNDs) are discoidal nanostructures that consist of a lipid bilayer membrane patch encased within membrane scaffold proteins (MSPs) derived from apolipoprotein A1. LNDs are playing increasingly important roles in studies of the structure and function of membrane proteins (MPs). A recent development is the use of styrene-maleic acid (SMA) copolymers for solubilization and reconstitution of MPs into nanodiscs. These polymer-encased nanodiscs (SMALPs, for SMA lipid particles) are promising platforms for studies of MPs in a near-physiologic environment without the use of detergents. However, current SMA copolymers display severe limitations in terms of buffer compatibility and ensued flexibility for various applications. In addition, the development of nanodiscs as a MP-supporting platform, or a drug targeting and delivery vehicle, is undermined by the fluidic and labile nature of the lipid bilayer. Here, we introduce new approaches to address some of the drawbacks of SMALPs and LNDs by using a set of new block copolymers to replace the MSPs and another set of block copolymers to replace the lipid bilayer. Our new family of zwitterionic styrene-maleic acid-derivative copolymers (zSMAs) do not aggregate at low pH or in the presence of polyvalent cations (as commercial SMAs do), and can be used to solubilize MPs and produce nanodiscs of controlled sizes. We also introduce polymer nanodiscs (PNDs), discoidal amphiphilic block copolymer membrane patches encased within MSPs. PNDs are novel two-dimensional nanomembranes that maintain the advantages of LNDs while addressing their stability weakness. We expect that the higher mechanical and chemical stability of block copolymer membranes and their chemical versatility for adaptation will open new opportunities for applications built upon diverse MP functions, or involved with drug targeting and delivery.