Animal Cryptochromes: Divergent Roles in Light Perception, Circadian Timekeeping and Beyond.
Animal Cryptochromes: Divergent Roles in Light Perception, Circadian Timekeeping and Beyond.
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DOI：
10.1111/php.12677
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发表时间：
2017-01
影响因子：
3.3
通讯作者：
Partch CL
中科院分区：
文献类型：
--
作者：
Michael AK;Fribourgh JL;Van Gelder RN;Partch CL
隐花色素在进化上与光依赖性 DNA 修复酶光裂合酶相关，是昆虫和脊椎动物昼夜节律的主要调节剂。动物界中有两种类型的隐花色素：类果蝇的 CRY，作为将昼夜节律与环境光/暗循环联系起来的非视觉感光色素；类脊椎动物的 CRY，似乎不直接感知光，但通过充当转录抑制子来控制昼夜节律的产生。有些动物同时具有两种类型的 CRY，而其他动物则只有一种。隐花色素有两个结构域：光裂合酶同源区 (PHR) 和延伸的、本质上无序的 C 末端。虽然所有动物 CRY 在其 PHR 结构域中都具有高度的序列和结构同源性，但 C 末端在长度和序列同一性方面存在差异。最近，隐花色素的功能已被证明超出了其在生物钟中的关键作用，参与了 DNA 损伤反应、癌症进展和糖皮质激素信号传导的调节，并被认为可能是磁感受器。在这篇综述中，我们提供了动物隐花色素发现的历史视角，研究了两种动物隐花色素的异同，并探讨了此类蛋白质的一些不同作用。隐花色素 (PDB: 4K0R) 的结构与光裂合酶类似，可调节动物的昼夜节律。左图，光吸收导致果蝇 CRY (dCRY) 发生构象变化，从而调节其与 TIM 的相互作用以实现昼夜节律光夹带。小鼠隐花色素 (mCRY) 独立于光抑制 CLOCK:BMAL1，以控制昼夜节律转录-翻译反馈环路。是的，CRY 也被提议充当光依赖性磁感受器。
Cryptochromes are evolutionarily related to the light-dependent DNA repair enzyme photolyase, serving as major regulators of circadian rhythms in insects and vertebrate animals. There are two types of cryptochromes in the animal kingdom: Drosophila-like CRYs that act as non-visual photopigments linking circadian rhythms to the environmental light/dark cycle, and vertebrate-like CRYs that do not appear to sense light directly, but control the generation of circadian rhythms by acting as transcriptional repressors. Some animals have both types of CRYs, while others possess only one. Cryptochromes have two domains, the photolyase homology region (PHR) and an extended, intrinsically disordered C-terminus. While all animal CRYs share a high degree of sequence and structural homology in their PHR domains, the C-termini are divergent in both length and sequence identity. Recently, cryptochrome function has been shown to extend beyond its pivotal role in circadian clocks, participating in regulation of the DNA damage response, cancer progression, and glucocorticoid signaling, as well as being implicated as possible magnetoreceptors. In this review, we provide a historical perspective on the discovery of animal cryptochromes, examine similarities and differences of the two types of animal cryptochromes, and explore some of the divergent roles for this class of proteins. Structurally similar to photolyase, cryptochromes (PDB: 4K0R) regulate circadian rhythms in animals. Left, light absorption leads to a conformational change in Drosophila CRY (dCRY) that regulates its interaction with TIM forcircadian photoentrainment. Mouse cryptochromes (mCRY) repress CLOCK:BMAL1 independently of light to control the circadian transcription-translation feedback loop. Right, CRYs have also been proposed to act as light-dependent magnetoreceptors.