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Unraveling the nature of the segmentation clock: Intrinsic disorder of clock proteins and their interaction map

机译:揭示分段时钟的本质:时钟蛋白的内在疾病及其相互作用图

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摘要

Vertebrate segmentation has been proved to be under a strict temporal control governed by a biological clock, known as the segmentation clock. The present experimental evidence suggests that the segmentation clock initiates and maintains its periodic cycle by the periodic activation or inhibition of the Notch signaling pathway as well as the periodic autoregulation of the cyclic genes themselves. In this paper, we investigate the structural and evolutionary properties of the Notch pathway proteins involved in the mice segmentation clock and computationally identify the interaction map within the Notch signaling pathway. The results of our analysis strongly indicate that most of the pathway proteins are intrinsically disordered and that the mechanism of their interaction likely involves helical molecular recognition elements, short loosely structured segments within disordered regions which are directly involved in protein–protein interactions. Predicted interactions are in agreement with gene knock-out studies available in the literature.
机译:椎骨分割已被证明受严格的时间控制,该时间由生物学时钟(称为分割时钟)控制。目前的实验证据表明,分段时钟通过Notch信号通路的周期性激活或抑制以及循环基因本身的周期性自动调节来启动并维持其周期性循环。在本文中,我们研究了小鼠切分时钟中涉及的Notch通路蛋白的结构和进化特性,并通过计算确定了Notch信号通路内的相互作用图。我们的分析结果有力地表明,大多数途径蛋白本质上都是无序的,它们相互作用的机制可能涉及螺旋分子识别元件,即无序区域内短松散的结构片段,直接参与蛋白-蛋白相互作用。预测的相互作用与文献中的基因敲除研究一致。

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