Interaction Dynamics of Intrinsically Disordered Proteins from Single-Molecule Spectroscopy.

IF 10.4 1区 生物学 Q1 BIOPHYSICS
Aritra Chowdhury, Daniel Nettels, Benjamin Schuler
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引用次数: 7

Abstract

Many proteins contain large structurally disordered regions or are entirely disordered under physiological conditions. The functions of these intrinsically disordered proteins (IDPs) often involve interactions with other biomolecules. An important emerging effort has thus been to identify the molecular mechanisms of IDP interactions and how they differ from the textbook notions of biomolecular binding for folded proteins. In this review, we summarize how the versatile tool kit of single-molecule fluorescence spectroscopy can aid the investigation of these conformationally heterogeneous and highly dynamic molecular systems. We discuss the experimental observables that can be employed and how they enable IDP complexes to be probed on timescales from nanoseconds to hours. Key insights include the diverse structural and dynamic properties of bound IDPs and the kinetic mechanisms facilitated by disorder, such as fly-casting; disorder-mediated encounter complexes; and competitive substitution via ternary complexes, which enables rapid dissociation even for high-affinity complexes. We also discuss emerging links to aggregation, liquid-liquid phase separation, and cellular processes, as well as current technical advances to further expand the scope of single-molecule spectroscopy.

从单分子光谱分析内在无序蛋白的相互作用动力学。
许多蛋白质含有大的结构紊乱区域或在生理条件下完全紊乱。这些内在无序蛋白(IDPs)的功能通常涉及与其他生物分子的相互作用。因此,一项重要的新兴工作是确定IDP相互作用的分子机制,以及它们与折叠蛋白质的生物分子结合的教科书概念有何不同。在这篇综述中,我们总结了单分子荧光光谱的多功能工具箱如何帮助研究这些构象异质和高动态的分子系统。我们讨论了可以使用的实验观测值,以及它们如何使IDP复合物能够在纳秒到小时的时间尺度上进行探测。关键的见解包括结合的IDPs的不同结构和动力学性质以及无序促进的动力学机制,例如飞铸;紊乱介导的偶遇复合物;通过三元配合物的竞争性取代,即使对高亲和力配合物也能快速解离。我们还讨论了聚集、液液相分离和细胞过程的新兴联系,以及进一步扩大单分子光谱范围的当前技术进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Annual Review of Biophysics
Annual Review of Biophysics 生物-生物物理
CiteScore
21.00
自引率
0.00%
发文量
25
期刊介绍: The Annual Review of Biophysics, in publication since 1972, covers significant developments in the field of biophysics, including macromolecular structure, function and dynamics, theoretical and computational biophysics, molecular biophysics of the cell, physical systems biology, membrane biophysics, biotechnology, nanotechnology, and emerging techniques.
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