Queueing up for enzymatic processing: correlated signaling through coupled degradation.

Queueing up for enzymatic processing: correlated signaling through coupled degradation.
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DOI:
10.1038/msb.2011.94
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发表时间:
2011-12-20
影响因子:
9.9
通讯作者:
--
中科院分区:
生物学1区
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--
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高通量技术已经导致产生复杂的布线图作为后测序范例,用于描绘巨大的和不同的细胞物种之间的相互作用。虽然这些图表对于大规模分析生物系统很有用,但详细了解所观察到的网络连接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,我们使用排队理论来研究“排队”如何导致蛋白质“客户”之间的相关性,这些客户仅通过一组下游的酶促“服务器”耦合。利用E. coliClpXP降解机作为一个模型处理系统,我们观察到显着的串扰之间的两个网络,通过一组共同的处理器间接耦合。我们进一步说明了使用合成生物学应用,其中两个独立的合成网络表现出同步行为时,常见的ClpXP机器不堪重负的酶促降解的影响。我们的研究结果表明,这样的翻译后过程可以导致动态连接的细胞网络,并可能提供一个现有的,但目前无法解释的链接的机械理解。
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.
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