Zhu Lingyun, Wang Yuxuan, Wu Xiaomin, Wu Guohua, Zhang Guohao, Liu Chuanyang, Zhang Shaowei
Department of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan 410073, China.
Comput Struct Biotechnol J. 2025 Feb 21;27:717-732. doi: 10.1016/j.csbj.2025.02.014. eCollection 2025.
Optogenetics has substantially enhanced our understanding of biological processes by enabling high-precision tracking and manipulation of individual cells. It relies on photosensitive proteins to monitor and control cellular activities, thereby paving the way for significant advancements in complex system research. Photosensitive proteins play a vital role in the development of optogenetics, facilitating the establishment of cutting-edge methods. Recent breakthroughs in protein design have opened up opportunities to develop protein-based tools that can precisely manipulate and monitor cellular activities. These advancements will significantly accelerate the development and application of optogenetic tools. This article emphasizes the pivotal role of protein design in the development of optogenetic tools, offering insights into potential future directions. We begin by providing an introduction to the historical development and fundamental principles of optogenetics, followed by an exploration of the operational mechanisms of key photosensitive domains, which includes clarifying the conformational changes they undergo in response to light, such as allosteric modulation and dimerization processes. Building on this foundation, we reveal the development of protein design tools that will enable the creation of even more sophisticated optogenetic techniques.
光遗传学通过实现对单个细胞的高精度追踪和操控,极大地增进了我们对生物过程的理解。它依靠光敏蛋白来监测和控制细胞活动,从而为复杂系统研究的重大进展铺平了道路。光敏蛋白在光遗传学的发展中起着至关重要的作用,推动了前沿方法的建立。蛋白质设计方面的最新突破为开发能够精确操控和监测细胞活动的基于蛋白质的工具带来了机遇。这些进展将显著加速光遗传学工具的开发和应用。本文强调了蛋白质设计在光遗传学工具开发中的关键作用,并对未来潜在的发展方向提供了见解。我们首先介绍光遗传学的历史发展和基本原理,接着探讨关键光敏结构域的作用机制,其中包括阐明它们在光响应下所经历的构象变化,如别构调节和二聚化过程。在此基础上,我们揭示了蛋白质设计工具的发展,这些工具将使更复杂的光遗传学技术得以创建。