Chemotaxis in Escherichia coli: a molecular model for robust precise adaptation.
Chemotaxis in Escherichia coli: a molecular model for robust precise adaptation.
复制标题
大肠杆菌中的趋化性：鲁棒精确适应的分子模型。
DOI：
10.1371/journal.pcbi.0040001
复制
发表时间：
2008-01
影响因子：
4.3
通讯作者：
Wingreen, Ned S.
中科院分区：
文献类型：
--
作者：
Hansen, Clinton H.;Endres, Robert G.;Wingreen, Ned S.
大肠杆菌中的趋化系统对多种化学信号在广泛的环境浓度范围内的浓度的微小相对变化非常敏感。受体之间的相互作用对于这种敏感性至关重要，因为精确的适应，在恒定的化学效应环境中，化学受体活性恢复到刺激前的水平。精确的适应依赖于化学受体分别通过CheR和CheB酶进行甲基化和去甲基化。实验表明，当与一个受体短暂结合时，这些酶作用于5到7个受体二聚体的小辅助邻域（AN）。在本文中，我们建立了一个强耦合的受体复合物模型，包括动态CheR和CheB作用于ANs，该模型在几个数量级的引诱剂浓度下产生敏感的反应和精确的适应，并解释了对天冬氨酸和丝氨酸的不同反应。在该模型中，我们探讨了适应的精度如何受到小AN尺寸以及CheR和CheB动力学（包括停留时间、饱和度和修饰位点之间的动力学差异）的限制，以及这些动力学如何在复杂活性中产生噪声。随机变化的生化参数证明了我们的动态模型精确适应的鲁棒性。细菌以相对直线的方式游动，并通过翻滚来改变方向。在趋化过程中，一个由受体和其他蛋白质组成的网络控制着翻滚的频率，从而引导它们随机地走向营养物质，远离驱避剂。受体聚类和通过共价修饰对持续刺激的适应使得趋化性在大范围的环境浓度下都是敏感的。趋化网络的各个组成部分被很好地表征，荧光显微镜的信号测量量化了网络的响应，使系统非常适合建模和分析。在本文中，我们扩展了先前基于实验的模型，表明适应所需的共价修饰是通过酶对邻近受体群（称为辅助邻域）的作用发生的。模拟表明，我们提出的强耦合受体复合物分子模型对不同的刺激产生准确的反应，并且对参数变化具有鲁棒性。在这个模型中，正确的适应反应受到小的辅助邻域大小和酶动力学的限制。我们还探讨了这些动力学如何在趋化反应中影响噪声。
The chemotaxis system in the bacterium Escherichia coli is remarkably sensitive to small relative changes in the concentrations of multiple chemical signals over a broad range of ambient concentrations. Interactions among receptors are crucial to this sensitivity as is precise adaptation, the return of chemoreceptor activity to prestimulus levels in a constant chemoeffector environment. Precise adaptation relies on methylation and demethylation of chemoreceptors by the enzymes CheR and CheB, respectively. Experiments indicate that when transiently bound to one receptor, these enzymes act on small assistance neighborhoods (AN) of five to seven receptor homodimers. In this paper, we model a strongly coupled complex of receptors including dynamic CheR and CheB acting on ANs. The model yields sensitive response and precise adaptation over several orders of magnitude of attractant concentrations and accounts for different responses to aspartate and serine. Within the model, we explore how the precision of adaptation is limited by small AN size as well as by CheR and CheB kinetics (including dwell times, saturation, and kinetic differences among modification sites) and how these kinetics contribute to noise in complex activity. The robustness of our dynamic model for precise adaptation is demonstrated by randomly varying biochemical parameters. Bacteria swim in relatively straight lines and change directions through tumbling. In the process of chemotaxis, a network of receptors and other proteins controls the tumbling frequency to direct an otherwise random walk toward nutrients and away from repellents. Receptor clustering and adaptation to persistent stimuli through covalent modification allow chemotaxis to be sensitive over a large range of ambient concentrations. The individual components of the chemotaxis network are well characterized, and signaling measurements by fluorescence microscopy quantify the network's response, making the system well suited for modeling and analysis. In this paper, we expand upon a previous model based on experiments indicating that the covalent modifications required for adaptation occur through the action of enzymes on groups of neighboring receptors, referred to as assistance neighborhoods. Simulations show that our proposed molecular model of a strongly coupled complex of receptors produces accurate responses to different stimuli and is robust to parameter variation. Within this model, the correct adaptation response is limited by small assistance-neighborhood size as well as enzyme kinetics. We also explore how these kinetics contribute to noise in the chemotactic response.
登录
查看更多内容
影响因子：
64.8
作者：
Alon, U;Surette, MG;Leibler, S
通讯作者：
Leibler, S
影响因子：
64.8
作者：
Barkai, N;Leibler, S
通讯作者：
Leibler, S
影响因子：
4.8
作者：
Levit, MN;Stock, JB
通讯作者：
Stock, JB
影响因子：
64.8
作者：
Kim, KK;Yokota, H;Kim, SH
通讯作者：
Kim, SH
DOI：
10.1073/pnas.092071899
发表时间：
2002-05-14
影响因子：
11.1
作者：
Ames, P;Studdert, CA;Parkinson, JS
通讯作者：
Parkinson, JS