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.
Department of Cell Biology and Genetics, Erasmus University Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
Inês
I
Chaves
Kazuhiro
K
Yagita
Sander
S
Barnhoorn
Hitoshi
H
Okamura
Gijsbertus T J
GT
van der Horst
Filippo
F
Tamanini
D056930:ARNTL Transcription Factors; D000595:Amino Acid Sequence; D000818:Animals; D029681:Arabidopsis Proteins / Q000378:metabolism; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D056926:CLOCK Proteins; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002940:Circadian Rhythm / Q000502:physiology*; D017124:Conserved Sequence; D056931:Cryptochromes; D004255:Deoxyribodipyrimidine Photo-Lyase / Q000378:metabolism; D019143:Evolution, Molecular; D005420:Flavoproteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D008322:Mammals; D051379:Mice; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins / Q000378:metabolism; D056950:Period Circadian Proteins; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D056930:ARNTL Transcription Factors; D029681:Arabidopsis Proteins; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D018797:Cell Cycle Proteins; D056931:Cryptochromes; D004255:Deoxyribodipyrimidine Photo-Lyase; D005420:Flavoproteins; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C538961:Bmal1 protein, mouse; C538964:Cry1 protein, mouse; C538967:Cry2 protein, mouse; C513312:Per2 protein, mouse; C538944:Clock protein, mouse