Improved Solubility of Membrane Proteins with zSMA Polymers
Improved Solubility of Membrane Proteins with zSMA Polymers
复制标题
使用 zSMA 聚合物提高膜蛋白的溶解度
DOI：
10.1016/j.bpj.2019.11.1418
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发表时间：
2020
影响因子：
3.4
通讯作者：
Liang, Hongjun
中科院分区：
文献类型：
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作者：
Fiori, Mariana C.;Jiang, Yunjiang;Zheng, Wan;Altenberg, Guillermo A.;Liang, Hongjun
苯乙烯-马来酸（SMA）共聚物已用于将膜蛋白（MP）溶解和重构成纳米盘。这些聚合物包裹的纳米盘（SMALPs; SMA脂质颗粒）是在接近生理环境中研究MP的有前途的平台。SMALP也可以从具有良好控制的组成的合成膜开始产生，用于研究脂质对MP的调节作用。SMA共聚物的一个缺点是它们对于各种应用的有限的缓冲液相容性和灵活性。我们先前证明，与SMA相反，我们的两性离子苯乙烯-马来酸衍生物共聚物（zSMA）在低pH或多价阳离子存在下不聚集，并且可用于溶解MP并产生受控尺寸的纳米盘。在这里，我们提出了不同的zSMA共聚物的增溶和稳定能力的数据。我们还通过从专门配制的蛋白脂质体中重构处于活性状态的MP来生产zSMAPL。我们预计，这组新的共聚物的化学多功能性将打开新的机会，应用建立在重建的MP，或涉及药物靶向和交付。这项工作得到了NSF赠款DMR-1623241和CBET-1623240的部分支持。
Styrene-maleic acid (SMA) copolymers have been used for solubilization and reconstitution of membrane proteins (MPs) into nanodiscs. These polymer-encased nanodiscs (SMALPs; SMA lipid particles) are a promising platform for studies of MPs in a near-physiologic environment. SMALPs can also be produced starting with synthetic membranes of well-controlled compositions for studies of the regulatory role of lipids on MPs. One drawback of the SMA copolymers is their limited buffer compatibility and flexibility for various applications. We previously demonstrated that in contrast to SMA, our zwitterionic styrene-maleic acid-derivative copolymers (zSMAs) do not aggregate at low pH or in the presence of polyvalent cations, and can be used to solubilize MPs and produce nanodiscs of controlled sizes. Here we present data on solubilization and stabilization capability of different zSMA copolymers. We also produce zSMAPLs by reconstitution of MPs in an active state from specifically formulated proteoliposomes. We expect that the chemical versatility of this new group of copolymers will open new opportunities for applications built on the reconstituted MPs, or involved with drug targeting and delivery. This work was supported in part by NSF grants DMR-1623241 and CBET-1623240.