A LOV2 Domain-Based Optogenetic Tool to Control Protein Degradation and Cellular Function
A LOV2 Domain-Based Optogenetic Tool to Control Protein Degradation and Cellular Function
复制标题
DOI：
10.1016/j.chembiol.2013.03.005
复制
发表时间：
2013-04-18
影响因子：
--
通讯作者：
Taxis, Christof
中科院分区：
文献类型：
--
作者：
Renicke, Christian;Schuster, Daniel;Taxis, Christof
光感知对于植物对外界信号的充分响应是必不可少的，并与关键转录调控因子的蛋白质分解有关。为了提供对蛋白质稳定性的合成光控制，我们开发了一个通用光敏降解(PSD)模块，将拟南芥PHY1的光反应LOV2结构域与小鼠鸟氨酸脱羧酶样降解序列cODC1结合在一起。PSD模块的功能在模式生物酿酒酵母中得到了演示。条件突变体的产生，细胞周期蛋白依赖性激酶活性的光调节，细胞生长的光模式，以及酵母摄影都是它的多功能性的例子。在对PSD模块行为进行计算机建模时，增加了对其特性的了解。这种经过工程改造的降解模块将光调节降解的原理传递给非植物生物。在生物技术或生物医学应用中控制蛋白质水平将是非常有益的，并提供了使过多的生物过程具有光开关的潜力。
Light perception is indispensable for plants to respond adequately to external cues and is linked to proteolysis of key transcriptional regulators. To provide synthetic light control of protein stability, we developed a generic photosensitive degron (psd) module combining the light-reactive LOV2 domain of Arabidopsis thaliana phot1 with the murine ornithine decarboxylase-like degradation sequence cODC1. Functionality of the psd module was demonstrated in the model organism Saccharomyces cerevisiae. Generation of conditional mutants, light regulation of cyclin-dependent kinase activity, light-based patterning of cell growth, and yeast photography exemplified its versatility. In silico modeling of psd module behavior increased understanding of its characteristics. This engineered degron module transfers the principle of light-regulated degradation to nonplant organisms. It will be highly beneficial to control protein levels in biotechnological or biomedical applications and offers the potential to render a plethora of biological processes light-switchable.