美国布兰代斯大学Dorothee Kern小组发现从原始时钟到昼夜振荡器的演化机制。相关论文于2023年3月22日在线发表在《自然》杂志上。

研究人员调查了只含有KaiBC的类球红细菌（Rhodobacter sphaeroides）的原始昼夜钟，以阐明其内部工作原理，尽管缺少KaiA。利用X射线晶体学和冷冻电镜的组合，研究人员发现了一个新的KaiC的十二边形折叠，其中两个六聚体被12个螺旋的盘绕束固定在一起。这种相互作用是由KaiC的羧基末端延伸形成的，并作为一个古老的调节分子，后来被KaiA所取代。日间和夜间构象之间的盘绕线圈注册转变通过一个跨度超过140埃的长程异构网络与磷酸化位点相连。这些动力学数据确定白天和夜间之间ATP-ADP比率的差异是驱动时钟的环境线索。它们还揭示了揭示自我维持振荡器演化的机制细节。

据了解，昼夜节律在许多生物过程中起着至关重要的作用，只有三种原核生物蛋白才能构成一个真正的翻译后昼夜振荡器。三个Kai蛋白的演化史表明，KaiC是最古老的成员，也是时钟的核心成分。随后加入的KaiB和KaiA调节KaiC的磷酸化状态以实现时间同步。蓝藻中典型的KaiABC系统已被充分了解，但对只拥有KaiBC的更古老的系统所知甚少。然而，有报道说它们可能表现出一种基本的、类似沙漏的计时机制。

附：英文原文

Title: From primordial clocks to circadian oscillators

Author: Pitsawong, Warintra, Pdua, Ricardo A. P., Grant, Timothy, Hoemberger, Marc, Otten, Renee, Bradshaw, Niels, Grigorieff, Nikolaus, Kern, Dorothee

Issue&Volume: 2023-03-22

Abstract: Circadian rhythms play an essential part in many biological processes, and only three prokaryotic proteins are required to constitute a true post-translational circadian oscillator1. The evolutionary history of the three Kai proteins indicates that KaiC is the oldest member and a central component of the clock2. Subsequent additions of KaiB and KaiA regulate the phosphorylation state of KaiC for time synchronization. The canonical KaiABC system in cyanobacteria is well understood3,4,5,6, but little is known about more ancient systems that only possess KaiBC. However, there are reports that they might exhibit a basic, hourglass-like timekeeping mechanism7,8,9. Here we investigate the primordial circadian clock in Rhodobacter sphaeroides, which contains only KaiBC, to elucidate its inner workings despite missing KaiA. Using a combination of X-ray crystallography and cryogenic electron microscopy, we find a new dodecameric fold for KaiC, in which two hexamers are held together by a coiled-coil bundle of 12 helices. This interaction is formed by the carboxy-terminal extension of KaiC and serves as an ancient regulatory moiety that is later superseded by KaiA. A coiled-coil register shift between daytime and night-time conformations is connected to phosphorylation sites through a long-range allosteric network that spans over 140. Our kinetic data identify the difference in the ATP-to-ADP ratio between day and night as the environmental cue that drives the clock. They also unravel mechanistic details that shed light on the evolution of self-sustained oscillators.

DOI: 10.1038/s41586-023-05836-9

Source: https://www.nature.com/articles/s41586-023-05836-9