Department of Chemistry and Biochemistry, UC Santa Cruz, 1156 High Street, Santa Cruz, CA 95064, USA.
Department of Chemistry and Biochemistry, UC Santa Cruz, 1156 High Street, Santa Cruz, CA 95064, USA; Center for Circadian Biology, UC San Diego, 9500 Gilman Drive, MC 0116, La Jolla, CA 92093, USA.
Semin Cell Dev Biol. 2022 Jun;126:71-78. doi: 10.1016/j.semcdb.2021.04.012. Epub 2021 Apr 28.
Genetically encoded biological clocks are found broadly throughout life on Earth, where they generate circadian (about a day) rhythms that synchronize physiology and behavior with the daily light/dark cycle. Although the genetic networks that give rise to circadian timing are now fairly well established, our understanding of how the proteins that constitute the molecular 'cogs' of this biological clock regulate the intrinsic timing, or period, of circadian rhythms has lagged behind. New studies probing the biochemical and structural basis of clock protein function are beginning to reveal how assemblies of dedicated clock proteins form and evolve through post-translational regulation to generate circadian rhythms. This review will highlight some recent advances providing important insight into the molecular mechanisms of period control in mammalian clocks with an emphasis on structural analyses related to CK1-dependent control of PER stability.
广泛存在于地球上的生物,其体内的基因编码生物时钟生成大约以一天为周期的昼夜节律,使生理机能和行为与日常的明暗周期同步。尽管产生昼夜节律的基因网络已经相当成熟,但我们对于构成生物钟分子“齿轮”的蛋白质如何调节内在的昼夜节律时间(或周期)的理解却相对滞后。新的研究探讨了生物钟蛋白功能的生化和结构基础,开始揭示专门的时钟蛋白组装如何通过翻译后调控形成和进化,从而产生昼夜节律。本文综述了一些最新进展,重点介绍了与 CK1 依赖性 PER 稳定性调控相关的结构分析,为哺乳动物生物钟的分子机制和周期调控提供了重要的见解。