How Do DNA Molecular Springs Modulate Protein-Protein Interactions: Experimental and Theoretical Results.

IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Biochemistry Biochemistry Pub Date : 2024-12-17 Epub Date: 2024-12-03 DOI:10.1021/acs.biochem.4c00280
Kecheng Zhang, Jingze Duan, Cong Li, Chen Song, Zhixing Chen
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引用次数: 0

Abstract

Deoxyribonucleic acid (DNA) nanomachines have been widely exploited in enzyme activity regulation, protein crystallization, protein assembly, and control of the protein-protein interaction (PPI). Yet, the fundamental biophysical framework of DNA nanomachines in the case of regulating protein-protein interactions remains elusive. Here, we established a DNA nanospring-mCherry model with mCherry homodimers of different Kd. Using size exclusion chromatography and fluorescence polarization, we profiled the DNA nanospring-mediated manipulation of PPI as an entropy-reducing process. The energy transfer efficiency was a function of the length of the complementary sequence and the geometry of the DNA nanospring construction. With basic force analysis and physical chemistry calculation, we proposed a unified model of the correlation between the dissociation constant, local concentration, construction of DNA nanospring, and kinetics of protein dimerization. Overall, we demonstrated that the DNA nanospring-mCherry conjugate was a simple and practical model to analyze DNA-controlled protein-protein interaction.

DNA分子弹簧如何调节蛋白质-蛋白质相互作用:实验和理论结果。
脱氧核糖核酸(DNA)纳米机器已广泛应用于酶活性调控、蛋白质结晶、蛋白质组装和蛋白质-蛋白质相互作用(PPI)的控制。然而,在调节蛋白质-蛋白质相互作用的情况下,DNA纳米机器的基本生物物理框架仍然难以捉摸。在这里,我们用不同Kd的mCherry同型二聚体建立了DNA纳米弹簧-mCherry模型。利用尺寸排除色谱和荧光偏振,我们描述了DNA纳米弹簧介导的PPI操作作为一个熵降低过程。能量传递效率是互补序列长度和DNA纳米弹簧结构几何形状的函数。通过基本力分析和物理化学计算,我们提出了解离常数、局部浓度、DNA纳米弹簧的构建和蛋白质二聚化动力学之间的统一模型。总之,我们证明了DNA纳米弹簧- mcherry偶联物是一种简单实用的模型,用于分析DNA控制的蛋白质-蛋白质相互作用。
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
Biochemistry Biochemistry
Biochemistry Biochemistry 生物-生化与分子生物学
CiteScore
5.50
自引率
3.40%
发文量
336
审稿时长
1-2 weeks
期刊介绍: Biochemistry provides an international forum for publishing exceptional, rigorous, high-impact research across all of biological chemistry. This broad scope includes studies on the chemical, physical, mechanistic, and/or structural basis of biological or cell function, and encompasses the fields of chemical biology, synthetic biology, disease biology, cell biology, nucleic acid biology, neuroscience, structural biology, and biophysics. In addition to traditional Research Articles, Biochemistry also publishes Communications, Viewpoints, and Perspectives, as well as From the Bench articles that report new methods of particular interest to the biological chemistry community.
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