Simulated diffusion of phosphorylated CheY through the cytoplasm of Escherichia coli
Simulated diffusion of phosphorylated CheY through the cytoplasm of Escherichia coli
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DOI：
10.1128/jb.187.1.45-53.2005
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发表时间：
2005-01-01
影响因子：
3.2
通讯作者：
Bray, D
中科院分区：
文献类型：
--
作者：
Lipkow, K;Andrews, SS;Bray, D
我们描述了使用计算模型来研究细胞结构和大分子拥挤对大肠杆菌趋化性信号转导的影响。新开发的程序 Smoldyn 允许模拟结构化环境中大量单个分子的运动和相互作用（S. S. Andrews 和 D. Bray，Phys. Biol.，出版中）。利用 Smoldyn，我们构建了大肠杆菌细胞的三维模型，并检查了 CheYp 在控制条件下以及对引诱剂和驱避剂刺激的响应下从受体簇到鞭毛马达的扩散。我们的模拟与细胞游泳反应的实验观察结果非常吻合，并且与野生型和突变细胞中预期的扩散行为一致。新程序提供的高分辨率使我们能够计算细胞中单个 CheYp 分子的位点以及它们在不同细胞条件下的寿命分布。我们发现，对于位于细胞中不同位置的鞭毛马达来说，刺激和反应之间的时间延迟是不同的。我们探索了磷酸酶 CheZ 的不同可能位置，并显示了细胞中存在 CheYp 梯度的条件。将惰性块引入细胞质中，代表不可穿透的结构，如类核和大蛋白复合物，导致 CheYp 的表观扩散系数下降，并增强了马达之间的差异。这些和其他结果将作为未来实验的预测。
We describe the use of a computational model to study the effects of cellular architecture and macromolecular crowding on signal transduction in Escherichia coli chemotaxis. A newly developed program, Smoldyn, allows the movement and interaction of a large number of individual molecules in a structured environment to be simulated (S. S. Andrews and D. Bray, Phys. Biol., in press). With Smoldyn, we constructed a three-dimensional model of an E. coli cell and examined the diffusion of CheYp from the cluster of receptors to the flagellar motors under control conditions and in response to attractant and repellent stimuli. Our simulations agree well with experimental observations of cell swimming responses and are consistent with the diffusive behavior expected in wild-type and mutant cells. The high resolution available to us in the new program allows us to calculate the loci of individual CheYp molecules in a cell and the distribution of their lifetimes under different cellular conditions. We find that the time delay between stimulus and response differs for flagellar motors located at different positions in the cell. We explore different possible locations for the phosphatase CheZ and show conditions under which a gradient of CheYp exists in the cell. The introduction of inert blocks into the cytoplasm, representing impenetrable structures such as the nucleoid and large protein complexes, produces a fall in the apparent diffusion coefficient of CheYp and enhances the differences between motors. These and other results are left as predictions for future experiments.