Analysis of protein homeostatic regulatory mechanisms in perturbed environments at steady state
Analysis of protein homeostatic regulatory mechanisms in perturbed environments at steady state
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DOI：
10.1006/jtbi.2001.2536
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发表时间：
2002-03-21
影响因子：
2
通讯作者：
Lindahl, PA
中科院分区：
文献类型：
--
作者：
Sewell, C;Morgan, JJ;Lindahl, PA
对9种不同的蛋白质稳态调节机制进行了分析，以了解它们在被外部过程扰动时将通用蛋白P维持在设定点稳态浓度的特定范围内的能力，这些外部过程改变了P的产生和/或消耗的速率。稳态监管有效性是由“扰动空间”矩形区域内的面积定义的，其中轴对应于正、负扰动的比率。这一区域的大小根据构成动态平衡机制的调控元件的不同而不同。这些元件包括转录的基本负反馈控制(其中P在相对于其设定值较高的浓度下与编码它的基因G结合，从而抑制转录)，反馈效应器的多重顺序结合(两个P依次与G结合)，以及反馈效应器的二聚化(P-2二聚体与G结合)。两种动态平衡机制包括级联结构，一种具有平移反馈控制，另一种不具有平移反馈控制。另一种机制包括对磷降解的反馈控制。最后，两种机制说明了监管体系的局限性。一种缺乏所有调控元件(只包括不变的P合成和降解速率)，而另一种假定完全(布尔)调控，其中转录在[P]>；[P](Sp)处完全抑制，在[P]<；[P](Sp)处完全活跃。所有被评估的系统都是已知的，但这里开发的ANA分析表达式允许在它们之间进行定量比较。这些表达以大肠杆菌中平均蛋白质的典型值进行评估。讨论了通过链接半独立的监管模块来构建监管网络的方法。(C)2002爱思唯尔科学有限公司。保留所有权利。
Nine different protein homeostatic regulatory mechanisms were analysed for their ability to maintain a generic protein P within a specified range of a set-point steady-state concentration while perturbed by external processes that altered the rates at which P was produced and/or consumed. Steady state regulatory effectiveness was defined by the area within a rectangular region of "perturbation space", where axes correspond to rates of positive and negative perturbations. The size of this region differed in accordance with the regulatory elements composing the homeostatic mechanism. Such elements included basic negative feedback control of transcription (in which P, at some high concentration relative to its set-point value, binds to the gene G that encodes it, thereby inhibiting transcription), multiple sequential binding of a feedback effector (two P's bind sequentially to G), and dimerization of a feedback effector (a P-2 dimer binds to G). Two homeostatic mechanisms included a cascade structure, one with and one without translational feedback control. Another mechanism included feedback control of P degradation. Finally, two mechanisms illustrated the limits of regulatory systems. One lacked all regulatory elements (and included only an invariant rate of P synthesis and degradation) while the other assumed perfect (Boolean) regulation, in which transcription is completely inhibited at [P] > [P](sp) and is fully active at [P] < [P](sp). All of the systems evaluated are known, but the ana analytical expressions developed here allow quantitative comparisons between them. These expressions were evaluated at values typical of the average protein in Escherichia coli. A method for building regulatory networks by linking semi-independent regulatory modules is discussed. (C) 2002 Elsevier Science Ltd. All rights reserved.