Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, 80045, USA.
Adv Biol (Weinh). 2021 May;5(5):e2000234. doi: 10.1002/adbi.202000234. Epub 2021 Jan 14.
To reveal the underpinnings of complex biological systems, a variety of approaches have been developed that allow switchable control of protein function. One powerful approach for switchable control is the use of inducible dimerization systems, which can be configured to control activity of a target protein upon induced dimerization triggered by chemicals or light. Individually, many inducible dimerization systems suffer from pre-defined dynamic ranges and overwhelming sensitivity to expression level and cellular context. Such systems often require extensive engineering efforts to overcome issues of background leakiness and restricted dynamic range. To address these limitations, recent tool development efforts have explored overlaying dimerizer systems with a second layer of regulation. Albeit more complex, the resulting layered systems have enhanced functionality, such as tighter control that can improve portability of these tools across platforms.
为了揭示复杂生物系统的基础,已经开发了多种方法来实现对蛋白质功能的可切换控制。一种用于可切换控制的强大方法是使用诱导二聚化系统,该系统可以通过化学物质或光诱导的二聚化来控制目标蛋白的活性。许多诱导二聚化系统单独使用时存在预定义的动态范围和对表达水平和细胞环境的过度敏感的问题。这些系统通常需要大量的工程努力来克服背景泄漏和动态范围受限的问题。为了解决这些限制,最近的工具开发工作探讨了将二聚化系统与第二层调节叠加。虽然更复杂,但由此产生的分层系统具有增强的功能,例如更严格的控制,可以提高这些工具在不同平台上的可移植性。