Walters Sara H, Birchfield Aaron S, Fuglestad Brian
Department of Chemistry, Virginia Commonwealth University, Richmond, VA 23284, U.S.A.
Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, VA 23219, U.S.A.
Biochem Soc Trans. 2024 Dec 19;52(6):2499-2511. doi: 10.1042/BST20240830.
Reverse micelles (RMs) have emerged as useful tools for the study of membrane associated proteins. With a nanoscale water core surrounded by surfactant and solubilized in a non-polar solvent, RMs stand apart as a unique membrane model. While RMs have been utilized as tools to investigate the physical properties of membranes and their associated water, RMs also effectively house membrane associated proteins for a variety of studies. High-resolution protein NMR revealed a need for development of improved RM formulations, which greatly enhanced the use of RMs for aqueous proteins. Protein-optimized RM formulations enabled encapsulation of challenging membrane associated protein types, including lipidated proteins, transmembrane proteins, and peripheral membrane proteins. Improvements in biological accuracy of RMs using phospholipid-based surfactants has advanced their utility as a membrane mimetic even further, better matching the chemistry of the most common cellular membrane lipids. Natural lipid extracts may also be used to construct RMs and house proteins, resulting in a membrane model that better represents the complexity of biological membranes. Recent applications in high-resolution investigations of protein-membrane interactions and inhibitor design of membrane associated proteins have demonstrated the usefulness of these systems in addressing this difficult category of protein. Further developments of RMs as membrane models will enhance the breadth of investigations facilitated by these systems and will enhance their use in biophysical, structural, and drug discovery pursuits of membrane associated proteins. In this review, we present the development of RMs as membrane models and their application to structural and biophysical study of membrane proteins.
反胶束（RMs）已成为研究膜相关蛋白的有用工具。反胶束具有被表面活性剂包围并溶解在非极性溶剂中的纳米级水核，作为一种独特的膜模型脱颖而出。虽然反胶束已被用作研究膜及其相关水的物理性质的工具，但反胶束也能有效地容纳膜相关蛋白以进行各种研究。高分辨率蛋白质核磁共振揭示了开发改进的反胶束制剂的必要性，这极大地增强了反胶束在水性蛋白质研究中的应用。蛋白质优化的反胶束制剂能够封装具有挑战性的膜相关蛋白类型，包括脂化蛋白、跨膜蛋白和外周膜蛋白。使用基于磷脂的表面活性剂提高反胶束的生物学准确性，进一步提升了它们作为膜模拟物的效用，使其更符合最常见细胞膜脂质的化学性质。天然脂质提取物也可用于构建反胶束并容纳蛋白质，从而形成一个能更好地代表生物膜复杂性的膜模型。最近在蛋白质 - 膜相互作用的高分辨率研究和膜相关蛋白抑制剂设计中的应用，证明了这些系统在研究这类困难蛋白方面的有用性。反胶束作为膜模型的进一步发展将扩大这些系统所促进的研究范围，并增强它们在膜相关蛋白的生物物理、结构和药物发现研究中的应用。在这篇综述中，我们介绍了反胶束作为膜模型的发展及其在膜蛋白结构和生物物理研究中的应用。
