DNA-Regulated Multi-Protein Complement Control

IF 14.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of the American Chemical Society Pub Date : 2024-11-21 DOI:10.1021/jacs.4c11315

Yinglun Ma, Peter H. Winegar, C. Adrian Figg, Namrata Ramani, Alex J. Anderson, Kathleen Ngo, John F. Ahrens, Nikhil S. Chellam, Young Jun Kim, Chad A. Mirkin

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Abstract

In nature, the interactions between proteins and their complements/substrates can dictate complex functions. Herein, we explore how DNA on nucleic acid modified proteins can be used as scaffolds to deliberately control interactions with a peptide complement (by adjusting length, sequence, and rigidity). As model systems, split GFPs were covalently connected through DNA scaffolds (36–58 bp). Increasing the length or decreasing the rigidity of the DNA scaffold (through removal of the duplex) increases the extent of intramolecular protein binding (up to 7.5-fold) between these GFP fragments. Independent and dynamic control over functional outputs can also be regulated by DNA hybridization; a multi-protein (split CFP and YFP) architecture was synthesized and characterized by fluorescence. This ternary construct shows that DNA displacement strands in different stoichiometric ratios can be used deliberately to regulate competitive binding between two unique sets of proteins. These studies establish a foundation for creating new classes of biological machinery based upon the concept of DNA-regulated multi-protein complement control.

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DNA 调节的多蛋白补体控制

在自然界中，蛋白质与其补体/底物之间的相互作用可决定复杂的功能。在此，我们探讨了如何利用核酸修饰蛋白上的 DNA 作为支架，有意控制与肽补体的相互作用（通过调整长度、序列和硬度）。作为模型系统，分裂的 GFP 通过 DNA 支架（36-58 bp）共价连接。增加 DNA 支架的长度或降低其硬度（通过去除双链）可增加这些 GFP 片段之间的分子内蛋白质结合程度（最多 7.5 倍）。对功能输出的独立和动态控制也可以通过 DNA 杂交来调节；我们合成了一种多蛋白（CFP 和 YFP 分裂）结构，并用荧光对其进行了表征。这种三元结构表明，可以有意识地使用不同化学计量比的 DNA 置换链来调节两组独特蛋白质之间的竞争性结合。这些研究为基于 DNA 调节的多蛋白互补控制概念创建新型生物机制奠定了基础。

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

Journal of the American Chemical Society 化学-化学综合

CiteScore

24.40

自引率

6.00%

发文量

2398

审稿时长

1.6 months

期刊介绍： The flagship journal of the American Chemical Society, known as the Journal of the American Chemical Society (JACS), has been a prestigious publication since its establishment in 1879. It holds a preeminent position in the field of chemistry and related interdisciplinary sciences. JACS is committed to disseminating cutting-edge research papers, covering a wide range of topics, and encompasses approximately 19,000 pages of Articles, Communications, and Perspectives annually. With a weekly publication frequency, JACS plays a vital role in advancing the field of chemistry by providing essential research.