A connector of two-component regulatory systems promotes signal amplification and persistence of expression

A connector of two-component regulatory systems promotes signal amplification and persistence of expression
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DOI:
10.1073/pnas.0704462104
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发表时间:
2007-07-17
影响因子:
11.1
通讯作者:
Groisman, Eduardo A.
Groisman, Eduardo A.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kato, Akinori;Mitrophanov, Alexander Y.;Groisman, Eduardo A.

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生物体依赖于多种调控结构来控制基因转录。虽然特定架构的功能特性已被很好地理解,但新发现的监管设计的特性却无法轻易预测。一种新兴的设计依赖于连接双组分调节系统的小蛋白,这构成了细菌信号转导的主要形式。这些连接器使一个系统能够响应不同系统感知到的信号。为了了解这种连接器介导的架构的功能特性,我们研究了由沙门氏菌的PhoP依赖性连接器蛋白PmrD控制的途径,并将其与基因直接受转录因子PhoP调控的电路进行对比。与直接途径相比,PmrD介导的途径显示信号放大和表达的持续性。这两种途径的数学建模使我们能够确定负责信号放大的关键因素。
Organisms rely on a variety of regulatory architectures to control gene transcription. Whereas the functional characteristics of particular architectures are well understood, the properties of newly discovered regulatory designs cannot be easily predicted. One emerging design depends on small proteins that connect two-component regulatory systems, which constitute the dominant form of bacterial signal transduction. These connectors enable one system to respond to the signal perceived by a different system. To understand the functional properties of such connector-mediated architectures, we investigated the pathway controlled by the PhoP-dependent connector protein PmrD of Salmonella enterica and contrasted it to the circuit in which genes are regulated directly by the transcription factor PhoP. The PmrD-mediated pathway displayed both signal amplification and persistence of expression when compared with the direct pathway. Mathematical modeling of the two pathways allowed us to identify critical factors responsible for signal amplification.