Sanofi, Framingham, MA, U.S.A.
Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, U.S.A.
Biochem Soc Trans. 2018 Dec 17;46(6):1495-1504. doi: 10.1042/BST20180139. Epub 2018 Nov 21.
The use of styrene-maleic acid (SMA) for the purification of a wide range of membrane proteins (MPs) from both prokaryotic and eukaryotic sources has begun to make an impact in the field of MP biology. This method is growing in popularity as a means to purify and thoroughly investigate the structure and function of MPs and biological membranes. The amphiphilic SMA copolymer can effectively extract MPs directly from a native lipid bilayer to form discs ∼10 nm in diameter. The resulting lipid particles, or styrene-maleic acid lipid particles (SMALPs), contain SMA, protein and membrane lipid. MPs purified in SMALPs are able to retain their native structure and, in many cases, functional activity, and growing evidence suggests that MPs purified using SMA have enhanced thermal stability compared with detergent-purified proteins. The SMALP method is versatile and is compatible with a wide range of cell types across taxonomic domains. It can readily be adapted to replace detergent in many protein purification methods, often with only minor changes made to the existing protocol. Moreover, biophysical analysis and structural determination may now be a possibility for many large, unstable MPs. Here, we review recent advances in the area of SMALP purification and how it is affecting the field of MP biology, critically assess recent progress made with this method, address some of the associated technical challenges which may remain unresolved and discuss opportunities for exploiting SMALPs to expand our understanding of structural and functional properties of MPs.
从原核生物和真核生物来源中纯化广泛的膜蛋白（MPs）的苯乙烯-马来酸（SMA）的使用开始在 MP 生物学领域产生影响。这种方法作为一种纯化和深入研究 MPs 和生物膜的结构和功能的手段越来越受欢迎。两亲性 SMA 共聚物可以有效地从天然脂质双层中直接提取 MPs，形成直径约 10nm 的圆盘。得到的脂质颗粒，或苯乙烯-马来酸脂质颗粒（SMALPs），含有 SMA、蛋白质和膜脂质。在 SMALPs 中纯化的 MPs 能够保留其天然结构，并且在许多情况下保留其功能活性，越来越多的证据表明，与去污剂纯化的蛋白质相比，用 SMA 纯化的 MPs 具有增强的热稳定性。SMALP 方法用途广泛，适用于分类学领域的各种细胞类型。它可以很容易地替代许多蛋白质纯化方法中的去污剂，通常只需对现有方案进行微小的改动。此外，生物物理分析和结构测定现在可能成为许多大型不稳定 MPs 的一种可能性。在这里，我们回顾了 SMALP 纯化领域的最新进展以及它如何影响 MP 生物学领域，批判性地评估了该方法的最新进展，解决了一些可能仍未解决的相关技术挑战，并讨论了利用 SMALPs 扩展我们对 MPs 的结构和功能性质的理解的机会。
