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PDBsum entry 4k0r
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Circadian clock protein
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PDB id
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4k0r
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DOI no:
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Cell
153:1394-1405
(2013)
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PubMed id:
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Structures of Drosophila cryptochrome and mouse cryptochrome1 provide insight into circadian function.
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A.Czarna,
A.Berndt,
H.R.Singh,
A.Grudziecki,
A.G.Ladurner,
G.Timinszky,
A.Kramer,
E.Wolf.
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ABSTRACT
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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.
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');
}
}
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