| Structural highlights
Function
[CRY1_DROME] Blue light-dependent regulator that is the input of the circadian feedback loop. Has no photolyase activity for cyclobutane pyrimidine dimers or 6-4 photoproducts. Regulation of expression by light suggests a role in photoreception for locomotor activity rhythms. Functions, together with per, as a transcriptional repressor required for the oscillation of peripheral circadian clocks and for the correct specification of clock cells. Genes directly activated by the transcription factors Clock (Clk) and cycle (cyc) are repressed by cry. Necessary for light-dependent magnetosensitivity, an intact circadian system is not required for the magnetoreception mechanism to operate. Required for both the naive and trained responses to magnetic field, consistent with the notion that cry is in the input pathway of magnetic sensing.[1] [2] [3] [4] [5] [6] [7] [8] [9]
Publication Abstract from PubMed
Drosophila cryptochrome (dCRY) is a FAD-dependent circadian photoreceptor, whereas mammalian cryptochromes (CRY1/2) are integral clock components that repress mCLOCK/mBMAL1-dependent transcription. We report crystal structures of full-length dCRY, a dCRY loop deletion construct, and the photolyase homology region of mouse CRY1 (mCRY1). Our dCRY structures depict Phe534 of the regulatory tail in the same location as the photolesion in DNA-repairing photolyases and reveal that the sulfur loop and tail residue Cys523 plays key roles in the dCRY photoreaction. Our mCRY1 structure visualizes previously characterized mutations, an NLS, and MAPK and AMPK phosphorylation sites. We show that the FAD and antenna chromophore-binding regions, a predicted coiled-coil helix, the C-terminal lid, and charged surfaces are involved in FAD-independent mPER2 and FBXL3 binding and mCLOCK/mBMAL1 transcriptional repression. The structure of a mammalian cryptochrome1 protein may catalyze the development of CRY chemical probes and the design of therapeutic metabolic modulators.
Structures of Drosophila cryptochrome and mouse cryptochrome1 provide insight into circadian function.,Czarna A, Berndt A, Singh HR, Grudziecki A, Ladurner AG, Timinszky G, Kramer A, Wolf E Cell. 2013 Jun 6;153(6):1394-405. doi: 10.1016/j.cell.2013.05.011. PMID:23746849[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Emery P, So WV, Kaneko M, Hall JC, Rosbash M. CRY, a Drosophila clock and light-regulated cryptochrome, is a major contributor to circadian rhythm resetting and photosensitivity. Cell. 1998 Nov 25;95(5):669-79. PMID:9845369
- ↑ Okano S, Kanno S, Takao M, Eker AP, Isono K, Tsukahara Y, Yasui A. A putative blue-light receptor from Drosophila melanogaster. Photochem Photobiol. 1999 Jan;69(1):108-13. PMID:10063806
- ↑ Stanewsky R, Kaneko M, Emery P, Beretta B, Wager-Smith K, Kay SA, Rosbash M, Hall JC. The cryb mutation identifies cryptochrome as a circadian photoreceptor in Drosophila. Cell. 1998 Nov 25;95(5):681-92. PMID:9845370
- ↑ Egan ES, Franklin TM, Hilderbrand-Chae MJ, McNeil GP, Roberts MA, Schroeder AJ, Zhang X, Jackson FR. An extraretinally expressed insect cryptochrome with similarity to the blue light photoreceptors of mammals and plants. J Neurosci. 1999 May 15;19(10):3665-73. PMID:10233998
- ↑ Ceriani MF, Darlington TK, Staknis D, Mas P, Petti AA, Weitz CJ, Kay SA. Light-dependent sequestration of TIMELESS by CRYPTOCHROME. Science. 1999 Jul 23;285(5427):553-6. PMID:10417378
- ↑ Collins B, Mazzoni EO, Stanewsky R, Blau J. Drosophila CRYPTOCHROME is a circadian transcriptional repressor. Curr Biol. 2006 Mar 7;16(5):441-9. PMID:16527739 doi:S0960-9822(06)01043-8
- ↑ Berndt A, Kottke T, Breitkreuz H, Dvorsky R, Hennig S, Alexander M, Wolf E. A novel photoreaction mechanism for the circadian blue light photoreceptor Drosophila cryptochrome. J Biol Chem. 2007 Apr 27;282(17):13011-21. Epub 2007 Feb 12. PMID:17298948 doi:M608872200
- ↑ Gegear RJ, Casselman A, Waddell S, Reppert SM. Cryptochrome mediates light-dependent magnetosensitivity in Drosophila. Nature. 2008 Aug 21;454(7207):1014-8. doi: 10.1038/nature07183. Epub 2008 Jul 20. PMID:18641630 doi:10.1038/nature07183
- ↑ Hoang N, Schleicher E, Kacprzak S, Bouly JP, Picot M, Wu W, Berndt A, Wolf E, Bittl R, Ahmad M. Human and Drosophila cryptochromes are light activated by flavin photoreduction in living cells. PLoS Biol. 2008 Jul 1;6(7):e160. doi: 10.1371/journal.pbio.0060160. PMID:18597555 doi:10.1371/journal.pbio.0060160
- ↑ Czarna A, Berndt A, Singh HR, Grudziecki A, Ladurner AG, Timinszky G, Kramer A, Wolf E. Structures of Drosophila cryptochrome and mouse cryptochrome1 provide insight into circadian function. Cell. 2013 Jun 6;153(6):1394-405. doi: 10.1016/j.cell.2013.05.011. PMID:23746849 doi:10.1016/j.cell.2013.05.011
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