Integrating ELF4 into the circadian system through combined structural and functional studies
Integrating ELF4 into the circadian system through combined structural and functional studies
复制标题
DOI：
10.2976/1.3218766
复制
发表时间：
2009-10-01
期刊：
影响因子：
--
通讯作者：
Davis, Seth J.
中科院分区：
文献类型：
--
作者：
Kolmos, Elsebeth;Nowak, Monika;Davis, Seth J.
生物钟是一种计时机制，可以预测每天的环境变化。在植物拟南芥中，昼夜节律系统是一系列互锁的转录-翻译反馈的多环。在这些振荡环中已经排列了几个基因，但核心时钟基因ELF4在这个网络中的位置以前尚未确定。ELF4与已知结构域缺乏序列相似性，功能同源物尚未鉴定。在这里，我们表明，ELF4是功能上保守的相关序列的一个分支内，并形成一个可能的静电接口，可以在结构上建模的α-螺旋同源二聚体。我们支持这一假设的表达分析新的elf4亚型等位基因。发现这些弱突变体具有早晨和晚上时钟基因的表达水平表型，暗示ELF 4在多环网络内有多个入口点。这可以用数学建模。此外，早晨表达的缺陷是特定的一些elf4等位基因，这表明主要的ELF4行动就在黎明前。我们提出了一个关于ELF 4在生物钟中作用的新假说：它作为一个同源二聚体整合了生物钟的两个臂。[DOI：10.2976/1.3218766]
The circadian clock is a timekeeping mechanism that enables anticipation of daily environmental changes. In the plant Arabidopsis thaliana, the circadian system is a multiloop series of interlocked transcription-translation feedbacks. Several genes have been arranged in these oscillation loops, but the position of the core-clock gene ELF4 in this network was previously undetermined. ELF4 lacks sequence similarity to known domains, and functional homologs have not yet been identified. Here we show that ELF4 is functionally conserved within a subclade of related sequences, and forms an alpha-helical homodimer with a likely electrostatic interface that could be structurally modeled. We support this hypothesis by expression analysis of new elf4 hypomorphic alleles. These weak mutants were found to have expression level phenotypes of both morning and evening clock genes, implicating multiple entry points of ELF4 within the multiloop network. This could be mathematically modeled. Furthermore, morning-expression defects were particular to some elf4 alleles, suggesting predominant ELF4 action just preceding dawn. We provide a new hypothesis about ELF4 in the oscillator-it acts as a homodimer to integrate two arms of the circadian clock. [DOI: 10.2976/1.3218766]