密码无时结构揭示了昼夜时钟的计时机制
Changfan Lin1, Shi Feng1, Cristina C DeOliveira1
1Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA.
Nature
|April 26, 2023
概括
的生理时钟
科学领域:
- 生物节律的分子机制
- 生物钟蛋白的结构生物学
- 昆虫的生理和适应
背景情况:
- 循环节律通过基因表达振荡来调节行为和疾病.
- 在中,无时代 (Tim) 调解周期 (Per) 的核入口,而加密色 (Cry) 则触发光中的时代降解.
- 了解生物钟中的分子相互作用对于解读其调节作用至关重要.
研究的目的:
- 阐明Cryptochrome对其目标Timeless的结构基础.
- 调查光感应Cryptochrome如何与时间无限互动,
- 探索无时间多态的结构机制及其适应不同气候.
主要方法:
- 低温电子显微镜 (cryo-EM) 的加密无时复合体.
- 蛋白质与蛋白质相互作用和辅因子结合的结构分析.
- 研究蛋白质化在核进口监管中的作用.
主要成果:
- 它连接到一个连续的无时重复和一个C端的Tim螺旋.
- 克莱的黄素辅因子经历了形状变化,在分子界面引发了大规模的重组.
- 一个酸化的Tim片段可能调节Importin-α结合,影响Tim-Per核进口.
- 蒂姆的N端插入重组的Cry口袋,取代光释放的C端尾部.
结论:
- 这项研究揭示了光感应Cryptochrome识别和与Timeless交互的分子机制.
- 结构洞察力解释了如何通过加密染色体介导的无时降解调节了的生理时钟.
- 这些发现为无时的多态化提供了结构基础,解释了适应多样化的气候.
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