Effects of adaptation in maintaining high sensitivity over a wide range of backgrounds for Escherichia coli chemotaxis
Effects of adaptation in maintaining high sensitivity over a wide range of backgrounds for Escherichia coli chemotaxis
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DOI：
10.1529/biophysj.106.097808
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发表时间：
2007-04-01
影响因子：
3.4
通讯作者：
Tu, Yuhai
中科院分区：
文献类型：
--
作者：
Mello, Bernardo A.;Tu, Yuhai
建立了一个变构模型，研究了不同MeAsp浓度下野生型大肠杆菌细胞对MeAsp的协同激酶反应。该模型结合wt剂量反应数据揭示了E.大肠杆菌的能力，以保持高灵敏度在广泛的背景。我们发现：适应性将系统调整到剂量响应曲线的最陡峭部分，其中对给定类型的刺激的敏感性通过（混合）功能性受体复合物中相应受体的数量而放大。从测量的灵敏度获得复合物N-a中焦油受体二聚体（N-a）的数目的下限大于或接近6。2），准确的适应性调节来自单个细胞中不同（未偶联的）受体复合物的激酶活性，并且对于维持（群体平均）激酶响应曲线中的高希尔系数至关重要。3），在我们的模型中，高灵敏度的宽动态范围可以通过在非活性和活性受体的配体解离常数之间具有非常小的比率C = 0.006，N-a = 6，和（甲基化水平无关的）非活性Tar受体的解离常数K = 18.2 μ M或通过具有K和/或或Na随着受体甲基化水平的升高而升高，且C > 0.01。具体的实验，建议区分这两种情况。4）野生型细胞中的受体占有率也应该适应并表现出对适应状态下配体浓度的缓慢（近似对数）依赖性;可以通过实验测试这种一般预测以验证/证伪我们的模型。
An allosteric model is developed to study the cooperative kinase response of wild-type ( wt) Escherichia coli cells to the chemoattractant MeAsp in different ambient MeAsp concentrations. The model, together with wt dose response data, reveals the underlying mechanism for E. coli's ability to maintain high sensitivity over a wide range of backgrounds. We find: 1), Adaptation tunes the system to the steepest part of the dose response curve, where the sensitivity to a given type of stimulus is amplified by the number of corresponding receptors in the ( mixed) functional receptor complex. A lower bound on the number of Tar receptor dimers ( N-a) in the complex N-a greater than or similar to 6 is obtained from the measured sensitivity. 2), Accurate adaptation synchronizes the kinase activities from different ( uncoupled) receptor complexes in a single cell and is crucial in maintaining the high Hill coefficient in the ( population averaged) kinase response curve. 3), The wide dynamic range of the high sensitivity can be explained in our model by either having a very small ratio between ligand dissociation constants of the inactive and the active receptors C = 0.006, N-a = 6, and a ( methylation level independent) dissociation constant for the inactive Tar receptor K = 18.2 mu M or by having K and/or Na increase with receptor methylation level together with a larger value of C > 0.01. Specific experiments are suggested to distinguish these two scenarios. 4), The receptor occupancy in a wt cell should also adapt and exhibit a slow ( approximately logarithmic) dependence on the ligand concentration in the adapted state; this general prediction can be tested experimentally to verify/falsify our model.