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.
Chaves
Inês
I
Department of Cell Biology and Genetics, Erasmus University Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
Yagita
Kazuhiro
K
Barnhoorn
Sander
S
Okamura
Hitoshi
H
van der Horst
Gijsbertus T J
GT
Tamanini
Filippo
F
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