Department of Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, United States; Department of Biology and Biological Engineering, Division of Chemical Biology, Chalmers Institute of Technology, 412 96 Gothenburg, Sweden.
Department of Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, United States.
Biochim Biophys Acta Proteins Proteom. 2019 Oct;1867(10):980-987. doi: 10.1016/j.bbapap.2019.04.007. Epub 2019 May 2.
Intrinsically disordered proteins (IDPs) are ubiquitous in proteomes and serve in a range of cellular functions including signaling, regulation, transport and enzyme function. IDP misfunction and aggregation are also associated with several diseases including neurodegenerative diseases and cancer. During the past decade, single-molecule methods have become popular for detailed biophysical and structural studies of these complex proteins. This work has included recent applications to cellular liquid-liquid phase separation (LLPS), relevant for functional dynamics of membraneless organelles such as the nucleolus and stress granules. In this concise review, we cover the conceptual motivations for development and application of single-molecule fluorescence methods for such IDP studies. We follow with a few key examples of systems and biophysical problems that have been addressed, and conclude with thoughts for emerging and future directions.
无规卷曲蛋白（IDP）在蛋白质组中普遍存在，在信号转导、调控、运输和酶功能等多种细胞功能中发挥作用。IDP 的功能障碍和聚集也与包括神经退行性疾病和癌症在内的几种疾病有关。在过去的十年中，单分子方法已成为研究这些复杂蛋白质的详细生物物理和结构的热门方法。这些工作包括最近在细胞液-液相分离（LLPS）方面的应用，这与无膜细胞器（如核仁、应激颗粒）的功能动力学相关。在这篇简明的综述中，我们介绍了为 IDP 研究开发和应用单分子荧光方法的概念性动机。随后我们介绍了一些已解决的系统和生物物理问题的关键实例，并对新兴和未来的方向进行了思考。
