Basu Roy Tanaya, Heidari Mana, Dokholyan Nikolay V
Department of Neurology, University of Virginia, School of Medicine, Charlottesville, VA, 22903, United States.
Department of Neuroscience & Experimental Therapeutics, Penn State College of Medicine, Hershey, PA, 17033, USA.
Curr Opin Struct Biol. 2025 Aug 5;94:103126. doi: 10.1016/j.sbi.2025.103126.
Optogenetically regulated enzymes offer unprecedented spatiotemporal control over protein activity, intermolecular interactions, and intracellular signaling. Many design strategies have been developed for their fabrication based on the principles of intrinsic allostery, oligomerization or 'split' status, intracellular compartmentalization, and steric hindrance. In addition to employing photosensory domains as part of the traditional optogenetic toolset, the specificity of effector domains has also been leveraged for endogenous applications. Here, we discuss the dynamics of light activation while providing a bird's eye view of the crafting approaches, targets, and impact of optogenetic enzymes in orchestrating cellular functions, as well as the bottlenecks and an outlook into the future.
光遗传学调控的酶为蛋白质活性、分子间相互作用和细胞内信号传导提供了前所未有的时空控制。基于内在变构、寡聚化或“分裂”状态、细胞内区室化和空间位阻原理，已经开发了许多用于其制造的设计策略。除了将光感域用作传统光遗传学工具集的一部分外，效应域的特异性也已用于内源性应用。在这里，我们讨论光激活的动力学，同时鸟瞰光遗传学酶在协调细胞功能中的构建方法、靶点和影响，以及瓶颈和未来展望。
