Roy Sourav, Schnell Santiago, Radivojac Predrag
Indiana University School of Informatics, 1900 East Tenth Street, Bloomington, IN 47406, USA.
Comput Biol Chem. 2006 Aug;30(4):241-8. doi: 10.1016/j.compbiolchem.2006.04.005. Epub 2006 Jun 22.
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.
脊椎动物的体节形成已被证明受到一个严格的生物钟控制，这个生物钟被称为体节时钟。目前的实验证据表明，体节时钟通过Notch信号通路的周期性激活或抑制以及循环基因自身的周期性自动调节来启动和维持其周期性循环。在本文中，我们研究了参与小鼠体节时钟的Notch信号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谱。我们的分析结果强烈表明，该信号通路中的大多数蛋白是内在无序的，并且它们的相互作用机制可能涉及螺旋分子识别元件，即无序区域内直接参与蛋白质-蛋白质相互作用的短的松散结构片段。预测的相互作用与文献中可用的基因敲除研究结果一致。
