Ultrasonic Control of Protein Splicing by Split Inteins,Journal of the American Chemical Society

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Ultrasonic Control of Protein Splicing by Split Inteins
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2024-09-18 , DOI: 10.1021/jacs.4c08207
Chuanjiang He _{1,

2} , Yu Zhou _{1,

3} , Junlin Chen ₄ , Rostislav Vinokur ₁ , Fabian Kiessling ₄ , Andreas Herrmann _{1,

2}

Affiliation

Utilizing ultrasound as an external stimulus to remotely modulate the activity of proteins is an important aspect of sonopharmacology and establishes the basis for the emerging field of sonogenetics. Here, we describe an ultrasound-responsive protein splicing system that enables spatiotemporal control of split-intein-mediated protein ligation. The system utilizes engineered split inteins that are caged and can be activated by thrombin released from a high molar mass DNA-based carrier under focused ultrasound sonication. This approach represents a general method for controlling the functions of proteins of interest by ultrasound, as demonstrated here by the controlled synthesis of the superfolder green fluorescence protein (GFP) and calcitonin. Furthermore, calcitonin receptor-mediated signal transduction in cells was triggered by this system in vitro without harming cell viability. By expanding the sonogenetic toolbox with protein splicing technologies, this study provides a possible pathway to deploy ultrasound for remotely controlling a variety of protein functions in deep tissue in the future.

中文翻译：

通过分裂内含子进行蛋白质剪接的超声波控制

利用超声波作为外部刺激来远程调节蛋白质的活性是声药理学的一个重要方面，并为新兴的声遗传学领域奠定了基础。在这里，我们描述了一种超声响应蛋白质剪接系统，该系统能够对分裂内含肽介导的蛋白质连接进行时空控制。该系统利用工程化的分裂内含肽，这些内含肽被笼住，并可以在聚焦超声处理下被高摩尔质量 DNA 载体释放的凝血酶激活。这种方法代表了通过超声控制感兴趣的蛋白质功能的通用方法，如超级文件夹绿色荧光蛋白（GFP）和降钙素的受控合成所证明的。此外，该系统在体外触发细胞中降钙素受体介导的信号转导，而不损害细胞活力。通过利用蛋白质剪接技术扩展声遗传学工具箱，这项研究为未来部署超声波远程控制深层组织中的各种蛋白质功能提供了一条可能的途径。

更新日期：2024-09-18

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