Bray D, Bourret R B
Department of Zoology, University of Cambridge, United Kingdom.
Mol Biol Cell. 1995 Oct;6(10):1367-80. doi: 10.1091/mbc.6.10.1367.
The chemotactic response of bacteria is mediated by complexes containing two molecules each of a transmembrane receptor and the intracellular signaling proteins CheA and CheW. Mutants in which one or the other of the proteins of this complex are absent, inactive, or expressed at elevated amounts show altered chemotactic behavior and the phenotypes are difficult to interpret for some overexpression mutants. We have examined the possibility that these unexpected phenotypes might arise from the binding steps that lead to active complex formation. A limited genetic algorithm was used to search for sets of binding reactions and associated binding constants expected to give mutant phenotypes in accord with experimental data. Different sets of binding equilibria and different assumptions about the activity of particular receptor complexes were tried. Computer analysis demonstrated that it is possible to obtain sets of binding equilibria consistent with the observed phenotypes and provided a simple explanation for these phenotypes in terms of the distribution of active and inactive complexes formed under various conditions. Optimization methods of this kind offer a unique way to analyze reactions taking place inside living cells based on behavioral data.
细菌的趋化反应由复合物介导，该复合物包含两个跨膜受体分子以及细胞内信号蛋白CheA和CheW各两个分子。在这些复合物中，若其中一种或另一种蛋白质缺失、无活性或过量表达，突变体则会表现出趋化行为改变，而对于一些过表达突变体，其表型难以解释。我们研究了这些意外表型可能源于导致活性复合物形成的结合步骤的可能性。使用了一种有限遗传算法来搜索预期能根据实验数据给出突变体表型的结合反应集和相关结合常数。尝试了不同的结合平衡集以及关于特定受体复合物活性的不同假设。计算机分析表明，有可能获得与观察到的表型一致的结合平衡集，并根据在各种条件下形成的活性和非活性复合物的分布为这些表型提供了一个简单的解释。这种优化方法为基于行为数据分析活细胞内发生的反应提供了一种独特的方式。
