Laboratory of Protein Design and Immunoengineering (LPDI), STI, EPFL, Lausanne, Switzerland.
Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.
Protein Sci. 2023 Oct;32(10):e4774. doi: 10.1002/pro.4774.
Small-molecule responsive protein switches are powerful tools for controlling cellular processes. These switches are designed to respond rapidly and specifically to their inducer. They have been used in numerous applications, including the regulation of gene expression, post-translational protein modification, and signal transduction. Typically, small-molecule responsive protein switches consist of two proteins that interact with each other in the presence or absence of a small molecule. Recent advances in computational protein design already contributed to the development of protein switches with an expanded range of small-molecule inducers and increasingly sophisticated switch mechanisms. Further progress in the engineering of small-molecule responsive switches is fueled by cutting-edge computational design approaches, which will enable more complex and precise control over cellular processes and advance synthetic biology applications in biotechnology and medicine. Here, we discuss recent milestones and how technological advances are impacting the development of chemical switches.
小分子响应蛋白开关是控制细胞过程的强大工具。这些开关设计为快速且特异性地响应其诱导剂。它们已被用于许多应用,包括基因表达的调控、翻译后蛋白质修饰和信号转导。通常,小分子响应蛋白开关由两种相互作用的蛋白质组成,在小分子的存在或不存在下。计算蛋白质设计的最新进展已经为具有扩展的小分子诱导剂范围和越来越复杂的开关机制的蛋白质开关的发展做出了贡献。小分子响应开关的工程学的进一步进展得益于前沿的计算设计方法,这将使细胞过程的控制更加复杂和精确,并推进生物技术和医学中的合成生物学应用。在这里,我们讨论了最近的里程碑以及技术进步如何影响化学开关的发展。