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From Proteopedia

Introduction

Cryptochromes are a category of flavoprotein photoreceptors that fall into the larger genetic family of photolyases/cryptochromes. The profoundly similar structure of these two proteins has led scientists to theorize that photolyases are the common ancestor of all cryptochromes.

Evolutionary History and Genetics of Cryptochrome Protein

Despite their shared genetic history, cryptochromes and photolyases have fundamentally different roles as proteins in species. Photolyases “utilize light energy for repair of UV-damaged DNA, either of photoproducts or of cyclobutane pyrimidine dimers.”^[1] Meanwhile, cryptochromes are responsible for the regulation of a handful of different biological processes. These two categories of proteins also differ in their abundance across the different kingdoms of organisms. While photolyases are nearly ubiquitous, being found even in some viruses, cryptochromes are mainly limited to animals and plants as well as a small number of other eukaryotes and prokaryotes. Thus, a general working definition for a cryptochrome is a photolyase-like protein that has lost its ability to repair DNA and subsequently gained ability to participate in signaling activity.^[2]

Variability Within the Family

Within the domain of cryptochromes there are several different variations both structurally and in terms of the role they play within the organism. The most basic division in cryptochrome types occurs between those found in plants and those found in animals. The first cryptochrome specimen to be studied intensively was found in the model plant Arabidopsis Thaliana. This cryptochrome, called cry1, was shown to inhibit specific growth functions upon exposure to blue lights. Further study revealed that there was also present a homologous protein, named cry2, that also played a part in circadian plant growth signaling.^[3]

The other large domain of cryptochrome proteins is defined by those found in animal organisms. These proteins are usually designated based upon their role in the circadian clock signaling it performs. Some of these proteins, called type I, are light responsive circadian photoreceptors. While others, type II, signal for circadian regulation via transcription-repression but are light-irresponsive. Importantly, but not without exception, type I proteins tend to be found in insects and type II usually are found in mammals and other vertebrates.^[4]

The animal distinctions of cryptochrome types is complicated by the fact that some species appear to contain both type I and II. One such example is the monarch butterfly. Here, the type I continues to operate as a light-activated molecular clock, but the type II operates as a signaler for sun compass navigation. Thus, type II cryptochromes have been shown to have a role in the migratory patterns of these insects.^[5]

Certainly, the diverse roles that cryptochromes can play in organisms proves the inherent complexity of biological systems. Yet, fundamentally cryptochromes are linked by their shared basic properties and genetic relationship with the older photolyases. In the Structure and Functions setting we will elucidate some of the over-arching mechanisms that tie together these apparently disparate properties.

Function

As indicated in the introduction, cryptochrome proteins have a variety of different roles in the many different organisms in which they occur. Perhaps one of the most studied functions of cryptochrome proteins is their role in circadian rhythms. Studies have shown that in drosophila, crypto chromes function as a FAD-dependent circadian photoreceptor. furthermore, mammalian cryptochromes similarly coordinated with an FAD cofactor in order to manage circadian functions, but by an alternate pathway. In mammals, the protein represses mCLOCK/mBMAL1-dependent transcription.^[6]

Although both drosophila and mammalian cryptochromes coordinate with an FAD cofactor in order to mediate circadian rhythms, their structure appears very different. Compare the two crystalized 3-D images of first the drosophila cryptochrome 1 with mammalian cryptochrome taken from mouse tissue.

References

1. ↑ Chaves, Inês, Richard Pokorny, Martin Byrdin, Nathalie Hoang, Thorsten Ritz, Klaus Brettel, Lars-Oliver Essen, Gijsbertus T. J. van der Horst, Alfred Batschauer, and Margaret Ahmad. “The Cryptochromes: Blue Light Photoreceptors in Plants and Animals.” Annual Review of Plant Biology 62, no. 1 (2011): 336.
2. ↑ Chaves, Inês, Richard Pokorny, Martin Byrdin, Nathalie Hoang, Thorsten Ritz, Klaus Brettel, Lars-Oliver Essen, Gijsbertus T. J. van der Horst, Alfred Batschauer, and Margaret Ahmad. “The Cryptochromes: Blue Light Photoreceptors in Plants and Animals.” Annual Review of Plant Biology 62, no. 1 (2011): 337
3. ↑ Ahmad M, Cashmore AR. 1993. Hy4 gene of A. thaliana encodes a protein with characteristics of a blue-light photoreceptor. Nature 366:162-166.
4. ↑ Chaves, Inês, Richard Pokorny, Martin Byrdin, Nathalie Hoang, Thorsten Ritz, Klaus Brettel, Lars-Oliver Essen, Gijsbertus T. J. van der Horst, Alfred Batschauer, and Margaret Ahmad. “The Cryptochromes: Blue Light Photoreceptors in Plants and Animals.” Annual Review of Plant Biology 62, no. 1 (2011): 354.
5. ↑ Gegear, Robert J., Lauren E. Foley, Amy Casselman, and Steven M. Reppert. "Animal cryptochromes mediate magnetoreception by an unconventional photochemical mechanism." Nature 463, no. 7282 (2010): 804-807.
6. ↑ Czarna, A et al. "Structures of Drosophila cryptochrome and mouse cryptochrome1 provide insight into circadian function." Cell 153, 1394-1405 (2013)