Functional evolution of the photolyase/cryptochrome protein family: importance of the C terminus of mammalian CRY1 for circadian core oscillator performance.
Cryptochromes (CRYs) are composed of a core domain with structural similarity to photolyase and a distinguishing C-terminal extension. While plant and fly CRYs act as circadian photoreceptors, using the C terminus for light signaling, mammalian CRY1 and CRY2 are integral components of the circadian oscillator. However, the function of their C terminus remains to be resolved. Here, we show that the C-terminal extension of mCRY1 harbors a nuclear localization signal and a putative coiled-coil domain that drive nuclear localization via two independent mechanisms and shift the equilibrium of shuttling mammalian CRY1 (mCRY1)/mammalian PER2 (mPER2) complexes towards the nucleus. Importantly, deletion of the complete C terminus prevents mCRY1 from repressing CLOCK/BMAL1-mediated transcription, whereas a plant photolyase gains this key clock function upon fusion to the last 100 amino acids of the mCRY1 core and its C terminus. Thus, the acquirement of different (species-specific) C termini during evolution not only functionally separated cryptochromes from photolyase but also caused diversity within the cryptochrome family.
|Keywords||*Evolution, Molecular, Amino Acid Sequence, Animals, Arabidopsis Proteins/metabolism, Base Sequence, Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism, Cell Cycle Proteins, Cell Nucleus/metabolism, Cells, Cultured, Circadian Rhythm/*physiology, Conserved Sequence, Deoxyribodipyrimidine Photo-Lyase/metabolism, Flavoproteins/genetics/*metabolism, Gene Expression Regulation, Mammals, Mice, Molecular Sequence Data, Nuclear Localization Signals, Nuclear Proteins/metabolism, Protein Structure, Tertiary, Protein Transport, Trans-Activators/genetics/metabolism, Transcription Factors/metabolism, Transcription, Genetic|
|Persistent URL||dx.doi.org/10.1128/MCB.26.5.1743-1753.2006, hdl.handle.net/1765/13981|
Chaves, I., Yagita, K., Barnhoorn, S., Okamura, H., van der Horst, G.T.J., & Tamanini, F.. (2006). Functional evolution of the photolyase/cryptochrome protein family: importance of the C terminus of mammalian CRY1 for circadian core oscillator performance.. Molecular and Cellular Biology, 26(5), 1743–1753. doi:10.1128/MCB.26.5.1743-1753.2006