Power of one: Investigating Protein Dynamic Functions using Single-Molecule Force Spectroscopy
Power of one: Investigating Protein Dynamic Functions using Single-Molecule Force Spectroscopy
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DOI：
10.13865/j.cnki.cjbmb.2017.10.01
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发表时间：
2017-10-01
期刊：
影响因子：
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通讯作者：
Chen Wei
中科院分区：
文献类型：
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作者：
An Chen-Yi;Fei Pan-Yu;Chen Wei
蛋白质的动态功能调节和决定细胞的生理和病理过程。它们不仅受蛋白质内在生化特性的调节，而且受体内复杂的生物力学微环境的影响。生物力学信号常与生物化学信号相结合，共同调控蛋白质相互作用、蛋白质构象和随后的信号转导。近年来，为了研究生物力学信号如何调控蛋白质动力学，单分子力谱（SMFS）技术的发展成功地突破了传统生化分析的局限，有效地揭示了蛋白质动力学及其调控机制。本文主要介绍了四种具有代表性的SMFS技术（原子力显微镜、光镊、生物膜力探针和磁镊），并重点介绍了它们在蛋白质动力学研究中的典型应用。此外，我们还介绍了常用的力谱分析，已被广泛应用沿着上述SMFS技术，精确定量的蛋白质-蛋白质相互作用的动力学（特别是蛋白质解离下的生物力学力）和构象变化。最后，展望了SMFS技术的发展方向，特别是探讨了如何将其他功能分析与SMFS技术相结合，以更全面地研究蛋白质的动态功能。希望本文的综述能为生物化学领域提供新的概念和工具，帮助更多的生物化学家更全面地研究蛋白质的动力学功能。
Dynamic functions of proteins regulate and determine the physiological and pathological processes of cells. They are not only regulated by protein's intrinsic biochemical characteristics, but also by complex biomechanical microenvironments in vivo. The biomechanical cues often couple with biochemical cues to cooperatively modulate dynamics of protein-protein interactions, protein conformations and subsequent signal transduction. Recently, in order to investigate how biomechanical cues regulate protein dynamics, single-molecule force spectroscopy (SMFS) has been developed to successfully break the limits of traditional biochemical assays, effectively revealing protein dynamics and their regulation mechanisms. In this review, we mainly introduce four representative SMFS techniques (atomic force microscopy, optical tweezers, biomembrane force probe and magnetic tweezers) in details, and focus on their typical applications in investigating most important aspects of protein dynamics. Additionally, we also introduce commonly used force-spectroscopy assays that have been extensively applied along with above SMFS techniques, to precisely quantify the kinetics of protein-protein interactions (especially protein dissociations under biomechanical force) and conformational changes. Finally, we briefly envision future direction of the development of SMFS techniques, especially discussing how to integrate other functional assays with SMFS to study the dynamic functions of proteins in a more comprehensive way. We hope this review provide new concepts and tools for the field of biochemistry to help more biochemists to study protein dynamic functions in a more comprehensive way.