Photoactivation of the cryptochrome/photolyase superfamily

The cryptochrome/photolyase superfamily is a class of flavoproteins that can regulate the growth and development in plants, as well as the circadian clock and the potential magnetic navigation in animals, primarily by absorbing UV-A and blue light. It is generally agreed that these functions depend on the photochemical reaction of the flavin adenine dinucleotide (FAD) chromophore, non-covalently binding to cryptochromes or photolyases. Irradiation can initiate either photoreduction between FAD and certain electron donors or electron jumping in FAD, thereby leading to the generation of intermediates that activate the protein. This signaling process is known as photoactivation. Subsequently, the activated protein will interact with downstream receptors to transfer the photo and magnetic signals. Based on in-depth research on photoactivation, two photo-cycle mechanisms for the photoreception/photosignaling of the cryptochrome/photolyase superfamily, i.e., the photolyase model and the phototropin model, have been proposed. There is no apparent alternative to the photo-cycle of cyclobutane pyrimidine dimer (CPD) or (6-4) photolyase following the photolyase model. However, the mechanism is not clear for the photoactivation of cryptochromes and CRY-DASH, a new subcategory of photolyase. Since the photoactivation process is the first step for the physiological function of proteins, more and improved research efforts in this field have been widely developed. This review first briefly presents the structure, the photoactivation, and the repair mechanism of CPD and (6-4) photolyase. Next, we review in detail the photoactivation of cryptochromes and CRY-DASH by analyzing the current status of research, as well as the contradictions in the resting redox states of FAD, intermediates in photoreactions, the photo-cycle of FAD, the signaling state of proteins, and the necessity of given tryptophans for protein activity. Based on these studies, the correlations of photoactivation and photo-cycle mechanisms, as well as the correlations of photoactivation and magnetoreception of proteins, are discussed. Finally the crucial open questions regarding the photoactivation mechanisms of the cryptochrome/photolyase superfamily are outlined, considering the hypothesis for a cryptochrome-based model of avian magnetoreception.