Chaves Inês, Yagita Kazuhiro, Barnhoorn Sander, Okamura Hitoshi, van der Horst Gijsbertus T J, Tamanini Filippo
Department of Cell Biology and Genetics, Erasmus University Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
Mol Cell Biol. 2006 Mar;26(5):1743-53. doi: 10.1128/MCB.26.5.1743-1753.2006.
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.
隐花色素（CRYs）由一个与光解酶结构相似的核心结构域和一个独特的C端延伸区组成。植物和果蝇的CRYs作为昼夜节律光感受器，利用C端进行光信号传导，而哺乳动物的CRY1和CRY2是昼夜节律振荡器的重要组成部分。然而，它们C端的功能仍有待确定。在这里，我们表明，mCRY1的C端延伸区含有一个核定位信号和一个假定的卷曲螺旋结构域，它们通过两种独立的机制驱动核定位，并使穿梭的哺乳动物CRY1（mCRY1）/哺乳动物PER2（mPER2）复合物的平衡向细胞核转移。重要的是，删除完整的C端会阻止mCRY1抑制CLOCK/BMAL1介导的转录，而一种植物光解酶在与mCRY1核心及其C端的最后100个氨基酸融合后获得了这种关键的生物钟功能。因此，在进化过程中获得不同的（物种特异性的）C端不仅在功能上使隐花色素与光解酶分离，而且还导致了隐花色素家族内部的多样性。
