Vertebrate Cryptochromes Are Vestigial Flavoproteins

Overview

Journal Sci Rep

Specialty Science

Date 2017 Mar 21

PMID 28317918

Citations 50

Authors

Roger J Kutta

Nataliya Archipowa

Linus O Johannissen

Alex R Jones

Nigel S Scrutton

Affiliations

Soon will be listed here.

Abstract

All cryptochromes are currently classified as flavoproteins. In animals their best-described role is as components of the circadian clock. This circadian function is variable, and can be either light-dependent or -independent; the molecular origin of this difference is unknown. Type I animal cryptochromes are photoreceptors that entrain an organism's clock to its environment, whereas Type II (including mammals) regulate circadian timing in a light-independent manner. Here, we reveal that, in contrast to Type I, Type II animal cryptochromes lack the structural features to securely bind the photoactive flavin cofactor. We provide a molecular basis for the distinct circadian roles of different animal cryptochromes, which also has significant implications for the putative role of Type II cryptochromes in animal photomagnetoreception.

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References

Foley L, Gegear R, Reppert S . Human cryptochrome exhibits light-dependent magnetosensitivity. Nat Commun. 2011; 2:356. PMC: 3128388. DOI: 10.1038/ncomms1364. View

Schmalen I, Reischl S, Wallach T, Klemz R, Grudziecki A, Prabu J . Interaction of circadian clock proteins CRY1 and PER2 is modulated by zinc binding and disulfide bond formation. Cell. 2014; 157(5):1203-15. DOI: 10.1016/j.cell.2014.03.057. View

Hattar S, Lucas R, Mrosovsky N, Thompson S, Douglas R, Hankins M . Melanopsin and rod-cone photoreceptive systems account for all major accessory visual functions in mice. Nature. 2003; 424(6944):76-81. PMC: 2885907. DOI: 10.1038/nature01761. View

YOUNG M, Kay S . Time zones: a comparative genetics of circadian clocks. Nat Rev Genet. 2001; 2(9):702-15. DOI: 10.1038/35088576. View

Laio A, Parrinello M . Escaping free-energy minima. Proc Natl Acad Sci U S A. 2002; 99(20):12562-6. PMC: 130499. DOI: 10.1073/pnas.202427399. View

Emery P, So W, Kaneko M, Hall J, Rosbash M . CRY, a Drosophila clock and light-regulated cryptochrome, is a major contributor to circadian rhythm resetting and photosensitivity. Cell. 1998; 95(5):669-79. DOI: 10.1016/s0092-8674(00)81637-2. View

Vaidya A, Top D, Manahan C, Tokuda J, Zhang S, Pollack L . Flavin reduction activates Drosophila cryptochrome. Proc Natl Acad Sci U S A. 2013; 110(51):20455-60. PMC: 3870761. DOI: 10.1073/pnas.1313336110. View

Yuan Q, Metterville D, Briscoe A, Reppert S . Insect cryptochromes: gene duplication and loss define diverse ways to construct insect circadian clocks. Mol Biol Evol. 2007; 24(4):948-55. DOI: 10.1093/molbev/msm011. View

Koenig T, Menze B, Kirchner M, Monigatti F, Parker K, Patterson T . Robust prediction of the MASCOT score for an improved quality assessment in mass spectrometric proteomics. J Proteome Res. 2008; 7(9):3708-17. DOI: 10.1021/pr700859x. View

10.

Berndt A, Kottke T, Breitkreuz H, Dvorsky R, Hennig S, Alexander M . A novel photoreaction mechanism for the circadian blue light photoreceptor Drosophila cryptochrome. J Biol Chem. 2007; 282(17):13011-21. DOI: 10.1074/jbc.M608872200. View

11.

Lamia K, Papp S, Yu R, Barish G, Uhlenhaut N, Jonker J . Cryptochromes mediate rhythmic repression of the glucocorticoid receptor. Nature. 2011; 480(7378):552-6. PMC: 3245818. DOI: 10.1038/nature10700. View

12.

Mouritsen H, Janssen-Bienhold U, Liedvogel M, Feenders G, Stalleicken J, Dirks P . Cryptochromes and neuronal-activity markers colocalize in the retina of migratory birds during magnetic orientation. Proc Natl Acad Sci U S A. 2004; 101(39):14294-9. PMC: 521149. DOI: 10.1073/pnas.0405968101. View

13.

Kume K, Zylka M, Sriram S, Shearman L, Weaver D, Jin X . mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop. Cell. 1999; 98(2):193-205. DOI: 10.1016/s0092-8674(00)81014-4. View

14.

Oostenbrink C, Villa A, Mark A, van Gunsteren W . A biomolecular force field based on the free enthalpy of hydration and solvation: the GROMOS force-field parameter sets 53A5 and 53A6. J Comput Chem. 2004; 25(13):1656-76. DOI: 10.1002/jcc.20090. View

15.

Legewie S, Herzel H, Westerhoff H, Bluthgen N . Recurrent design patterns in the feedback regulation of the mammalian signalling network. Mol Syst Biol. 2008; 4:190. PMC: 2424294. DOI: 10.1038/msb.2008.29. View

16.

Xing W, Busino L, Hinds T, Marionni S, Saifee N, Bush M . SCF(FBXL3) ubiquitin ligase targets cryptochromes at their cofactor pocket. Nature. 2013; 496(7443):64-8. PMC: 3618506. DOI: 10.1038/nature11964. View

17.

Moller A, Sagasser S, Wiltschko W, Schierwater B . Retinal cryptochrome in a migratory passerine bird: a possible transducer for the avian magnetic compass. Naturwissenschaften. 2004; 91(12):585-8. DOI: 10.1007/s00114-004-0578-9. View

18.

Hore P, Mouritsen H . The Radical-Pair Mechanism of Magnetoreception. Annu Rev Biophys. 2016; 45:299-344. DOI: 10.1146/annurev-biophys-032116-094545. View

19.

Pace C, Vajdos F, Fee L, Grimsley G, Gray T . How to measure and predict the molar absorption coefficient of a protein. Protein Sci. 1995; 4(11):2411-23. PMC: 2143013. DOI: 10.1002/pro.5560041120. View

20.

Ozgur S, Sancar A . Purification and properties of human blue-light photoreceptor cryptochrome 2. Biochemistry. 2003; 42(10):2926-32. DOI: 10.1021/bi026963n. View