Functional evolution of the photolyase/cryptochrome protein family: Importance of the C terminus of mammalian CRY1 for circadian core oscillator performance
Functional evolution of the photolyase/cryptochrome protein family: Importance of the C terminus of mammalian CRY1 for circadian core oscillator performance
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DOI：
10.1128/mcb.26.5.1743-1753.2006
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发表时间：
2006-03-01
影响因子：
5.3
通讯作者：
Tamanini, F
中科院分区：
文献类型：
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作者：
Chaves, I;Yagita, K;Tamanini, F
隐花色素（CRYs）由一个与光裂合酶具有结构相似性的核心结构域和一个独特的C末端延伸部分组成。植物和果蝇的隐花色素作为昼夜节律光感受器，利用C末端进行光信号传导，而哺乳动物的CRY1和CRY2是昼夜节律振荡器的组成部分。然而，它们C末端的功能仍有待阐明。在此，我们发现mCRY1的C末端延伸部分包含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，并使穿梭于细胞质和细胞核之间的哺乳动物CRY1（mCRY1）/哺乳动物PER2（mPER2）复合物的平衡向细胞核转移。重要的是，完全缺失C末端会使mCRY1无法抑制CLOCK/BMAL1介导的转录，而一种植物光裂合酶在与mCRY1的最后100个氨基酸（包括核心部分及其C末端）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末端不仅在功能上使隐花色素与光裂合酶分离，还导致了隐花色素家族内部的多样性。
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 dluring evolution not only functionally separated cryptochromes from photolyase but also caused diversity within the cryptochrome family.