A Design Principle for an Autonomous Post-translational Pattern Formation.
A Design Principle for an Autonomous Post-translational Pattern Formation.
复制标题
自主翻译后模式形成的设计原则。
DOI：
10.1016/j.celrep.2017.03.081
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发表时间：
2017
期刊：
影响因子：
8.8
通讯作者：
Ueda HR.
中科院分区：
文献类型：
--
作者：
Sugai S;Ode KL;Ueda HR.
以前的自主模式形成模型通常假设复杂的分子和细胞网络。然而，这项理论研究表明，由一个具有多位点磷酸化的底物和一对激酶和磷酸酶组成的系统可以生成自主空间信息，包括复杂的条纹图案。所有（去）磷酸化反应均采用通用 Michaelis-Menten 方案进行描述，并且所有物质均可自由扩散，无需预先存在梯度。对超过 23,000,000 个随机生成的参数集进行的计算模拟揭示了循环反应和慢扩散底物封存酶的设计主题。这些基序构成短程正反馈回路和长程负反馈回路，从而引起图灵不稳定性。空间图案的宽度和高度可以通过不同的反应扩散过程独立控制。因此，多位点可逆翻译后修饰可以成为各种模式的普遍来源，而不需要其他复杂的调节，例如酶的自催化调节，并且适用于诱导由翻译后修饰驱动的蛋白质亚细胞定位的分子机制。
Previous autonomous pattern-formation models often assumed complex molecular and cellular networks. This theoretical study, however, shows that a system composed of one substrate with multisite phosphorylation and a pair of kinase and phosphatase can generate autonomous spatial information, including complex stripe patterns. All (de-)phosphorylation reactions are described with a generic Michaelis-Menten scheme, and all species freely diffuse without pre-existing gradients. Computational simulation upon >23,000,000 randomly generated parameter sets revealed the design motifs of cyclic reaction and enzyme sequestration by slow-diffusing substrates. These motifs constitute short-range positive and long-range negative feedback loops to induce Turing instability. The width and height of spatial patterns can be controlled independently by distinct reaction-diffusion processes. Therefore, multisite reversible post-translational modification can be a ubiquitous source for various patterns without requiring other complex regulations such as autocatalytic regulation of enzymes and is applicable to molecular mechanisms for inducing subcellular localization of proteins driven by post-translational modifications.