Department of Chemistry and Biophysics, Biomedical Engineering, Macromolecular Science and Engineering, Michigan Neuroscience Institute, The University of Michigan, Ann Arbor, MI 48109-1055, USA.
Biomolecules. 2022 Aug 4;12(8):1076. doi: 10.3390/biom12081076.
Atomic-resolution structural studies of membrane-associated proteins and peptides in a membrane environment are important to fully understand their biological function and the roles played by them in the pathology of many diseases. However, the complexity of the cell membrane has severely limited the application of commonly used biophysical and biochemical techniques. Recent advancements in NMR spectroscopy and cryoEM approaches and the development of novel membrane mimetics have overcome some of the major challenges in this area. For example, the development of a variety of lipid-nanodiscs has enabled stable reconstitution and structural and functional studies of membrane proteins. In particular, the ability of synthetic amphipathic polymers to isolate membrane proteins directly from the cell membrane, along with the associated membrane components such as lipids, without the use of a detergent, has opened new avenues to study the structure and function of membrane proteins using a variety of biophysical and biological approaches. This review article is focused on covering the various polymers and approaches developed and their applications for the functional reconstitution and structural investigation of membrane proteins. The unique advantages and limitations of the use of synthetic polymers are also discussed.
在膜环境中对膜相关蛋白和肽进行原子分辨率结构研究对于充分了解它们的生物学功能以及它们在许多疾病的发病机制中的作用非常重要。然而，细胞膜的复杂性严重限制了常用生物物理和生化技术的应用。近年来，NMR 光谱和 cryoEM 方法的进展以及新型膜类似物的开发克服了该领域的一些主要挑战。例如，各种脂质纳米盘的开发使得能够稳定地重建和进行膜蛋白的结构和功能研究。特别是，合成两亲聚合物能够直接从细胞膜中分离膜蛋白，以及相关的膜成分（如脂质），而无需使用去污剂，这为使用各种生物物理和生物学方法研究膜蛋白的结构和功能开辟了新的途径。本文综述了各种聚合物和方法的开发及其在膜蛋白的功能重建和结构研究中的应用。还讨论了使用合成聚合物的独特优点和局限性。
