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首页> 外文期刊>Journal of Theoretical Biology >Analysis of Protein Homeostatic Regulatory Mechanisms in Perturbed Environments at Steady State.
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Analysis of Protein Homeostatic Regulatory Mechanisms in Perturbed Environments at Steady State.

机译:稳态下摄动环境中蛋白质稳态调节机制的分析。

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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 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. Copyright 2002 Elsevier Science Ltd. All rights reserved.
机译:分析了九种不同的蛋白质稳态调节机制的能力,这些机制可将通用蛋白质P维持在设定点稳态浓度的指定范围内,同时受到改变P产生和/或消耗速率的外部过程的干扰。稳态调节有效性由“扰动空间”的矩形区域内的区域定义,其中轴分别对应于正扰动和负扰动的比率。该区域的大小根据组成稳态机制的调节元件而不同。这些元素包括转录的基本负反馈控制(其中,相对于其设定点值高浓度的P与编码它的基因G结合,从而抑制转录),反馈效应子的多个顺序结合(两个P依次与G结合)和反馈效应器的二聚化(P(2)二聚体与G结合)。两种稳态方法包括级联结构,一种具有平移反馈控制,一种没有平移反馈控制。另一机制包括对P降解的反馈控制。最后,两种机制说明了监管体系的局限性。一个缺少所有调节元件(并且仅包括不变的P合成和降解速率),而另一个则假设是完美的(布尔)调节,其中转录在[P]> [P](sp)时被完全抑制,在[P]> [P](sp)时完全活跃[P] <[P](sp)。所有评估的系统都是已知的,但是此处开发的分析表达式可以对它们进行定量比较。在大肠杆菌中平均蛋白质的典型值下评估这些表达。讨论了一种通过链接半独立的监管模块来构建监管网络的方法。版权所有2002 Elsevier ScienceLtd。保留所有权利。

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