Light-Oxygen-Voltage (LOV)-sensing Domains: Activation Mechanism and Optogenetic Stimulation.

[Display omitted] • Light-oxygen-voltage (LOV) domains are flavin mononucleotide-binding, blue-light receptors. • They regulate cell responses via naturally attached/engineered effector proteins. • The elucidation of their photoreaction dynamics is a major bottleneck in their study. • LOV-based tools can be designed for light-controlled processes (e.g., optogenetic tools). • Advances in time-resolved crystallography, spectroscopy, and computational science will aid in resolving the photoreaction and developing optogenetic tools. The light-oxygen-voltage (LOV) domains of phototropins emerged as essential constituents of light-sensitive proteins, helping initiate blue light-triggered responses. Moreover, these domains have been identified across all kingdoms of life. LOV domains utilize flavin nucleotides as co-factors and undergo structural rearrangements upon exposure to blue light, which activates an effector domain that executes the final output of the photoreaction. LOV domains are versatile photoreceptors that play critical roles in cellular signaling and environmental adaptation; additionally, they can noninvasively sense and control intracellular processes with high spatiotemporal precision, making them ideal candidates for use in optogenetics, where a light signal is linked to a cellular process through a photoreceptor. The ongoing development of LOV-based optogenetic tools, driven by advances in structural biology, spectroscopy, computational methods, and synthetic biology, has the potential to revolutionize the study of biological systems and enable the development of novel therapeutic strategies. [ABSTRACT FROM AUTHOR]