细胞中肌动蛋白结合的开关蛋白
Turn-on protein switches for controlling actin binding in cells.
机构信息
McKetta Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, 78712, USA.
出版信息
Nat Commun. 2024 Jul 11;15(1):5840. doi: 10.1038/s41467-024-49934-2.
Within a shared cytoplasm, filamentous actin (F-actin) plays numerous and critical roles across the cell body. Cells rely on actin-binding proteins (ABPs) to organize F-actin and to integrate its polymeric characteristics into diverse cellular processes. Yet, the multitude of ABPs that engage with and shape F-actin make studying a single ABP's influence on cellular activities a significant challenge. Moreover, without a means of manipulating actin-binding subcellularly, harnessing the F-actin cytoskeleton for synthetic biology purposes remains elusive. Here, we describe a suite of designed proteins, Controllable Actin-binding Switch Tools (CASTs), whose actin-binding behavior can be controlled with external stimuli. CASTs were developed that respond to different external inputs, providing options for turn-on kinetics and enabling orthogonality and multiplexing. Being genetically encoded, we show that CASTs can be inserted into native protein sequences to control F-actin association locally and engineered into structures to control cell and tissue shape and behavior.
在细胞质中共存时,丝状肌动蛋白(F-actin)在整个细胞中发挥着众多关键作用。细胞依赖肌动蛋白结合蛋白(ABPs)来组织 F-actin 并将其聚合特性整合到各种细胞过程中。然而,与 F-actin 结合并塑造其形状的 ABPs 众多,使得研究单个 ABP 对细胞活动的影响成为一项重大挑战。此外,由于缺乏亚细胞操纵肌动蛋白结合的手段,因此仍然难以利用 F-actin 细胞骨架进行合成生物学应用。在这里,我们描述了一系列设计的蛋白质,即可控肌动蛋白结合开关工具(CASTs),其肌动蛋白结合行为可以通过外部刺激来控制。开发了对不同外部输入做出响应的 CASTs,为开启动力学提供了选择,并实现了正交性和多重性。由于 CASTs 是遗传编码的,我们表明可以将 CASTs 插入到天然蛋白质序列中以局部控制 F-actin 结合,或者将其设计到结构中以控制细胞和组织的形状和行为。