Molecular Biology Section, Division of Biological Science, University of California, San Diego, CA, USA.
Mol Syst Biol. 2011 Dec 20;7:561. doi: 10.1038/msb.2011.94.
High-throughput technologies have led to the generation of complex wiring diagrams as a post-sequencing paradigm for depicting the interactions between vast and diverse cellular species. While these diagrams are useful for analyzing biological systems on a large scale, a detailed understanding of the molecular mechanisms that underlie the observed network connections is critical for the further development of systems and synthetic biology. Here, we use queueing theory to investigate how 'waiting lines' can lead to correlations between protein 'customers' that are coupled solely through a downstream set of enzymatic 'servers'. Using the E. coli ClpXP degradation machine as a model processing system, we observe significant cross-talk between two networks that are indirectly coupled through a common set of processors. We further illustrate the implications of enzymatic queueing using a synthetic biology application, in which two independent synthetic networks demonstrate synchronized behavior when common ClpXP machinery is overburdened. Our results demonstrate that such post-translational processes can lead to dynamic connections in cellular networks and may provide a mechanistic understanding of existing but currently inexplicable links.
高通量技术产生了复杂的连线图，作为一种测序后的范例，用于描述庞大而多样化的细胞种类之间的相互作用。虽然这些图谱对于大规模分析生物系统很有用，但要深入了解观察到的网络连接背后的分子机制对于系统和合成生物学的进一步发展至关重要。在这里，我们使用排队论来研究“等待队列”如何导致仅通过下游一组酶“服务器”连接的蛋白质“客户”之间的相关性。使用大肠杆菌 ClpXP 降解机器作为模型处理系统，我们观察到两个网络之间存在显著的串扰，这两个网络通过一组共同的处理器间接耦合。我们进一步使用合成生物学应用说明了酶排队的影响，其中两个独立的合成网络在共同的 ClpXP 机械装置过载时表现出同步行为。我们的结果表明，这种翻译后过程可以导致细胞网络中的动态连接，并可能为现有但目前无法解释的联系提供机制理解。
