Design and engineering of light-sensitive protein switches.
Design and engineering of light-sensitive protein switches.
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DOI：
10.1016/j.sbi.2022.102377
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发表时间：
2022-06
影响因子：
6.8
通讯作者：
Kuhlman, Brian
中科院分区：
文献类型：
--
作者：
McCue, Amelia C.;Kuhlman, Brian
工程化的光敏蛋白质开关用于检测多种生物过程。这些开关通常是通过将天然存在的光响应蛋白结构域与其他蛋白的功能结构域进行基因融合而构建的。蛋白质活性可以通过多种机制来控制，包括光诱导共定位、笼养和变构调节。蛋白质设计工作的重点是减少背景信号传导、最大化光刺激下的活性变化以及扰乱转换动力学。通常将基于结构的建模与实验筛选相结合，以确定域之间的理想融合点并发现优化切换的点突变。在这里，我们介绍常用的光敏感结构域，并总结利用它们调节蛋白质活性的最新进展。
Engineered, light-sensitive protein switches are used to interrogate a broad variety of biological processes. These switches are typically constructed by genetically fusing naturally occurring light-responsive protein domains with functional domains from other proteins. Protein activity can be controlled using a variety of mechanisms including light-induced colocalization, caging, and allosteric regulation. Protein design efforts have focused on reducing background signaling, maximizing the change in activity upon light stimulation, and perturbing the kinetics of switching. It is common to combine structure-based modeling with experimental screening to identify ideal fusion points between domains and discover point mutations that optimize switching. Here, we introduce commonly used light-sensitive domains and summarize recent progress in using them to regulate protein activity.
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