4k03
Crystal structure of Drosophila Cryprochrome
Structural highlights
FunctionCRY1_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 PubMedDrosophila 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. See AlsoReferences
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