Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
EMBO J. 2011 May 4;30(9):1719-29. doi: 10.1038/emboj.2011.77. Epub 2011 Mar 25.
In chemotactic bacteria, transmembrane chemoreceptors, CheA and CheW form the core signalling complex of the chemotaxis sensory apparatus. These complexes are organized in extended arrays in the cytoplasmic membrane that allow bacteria to respond to changes in concentration of extracellular ligands via a cooperative, allosteric response that leads to substantial amplification of the signal induced by ligand binding. Here, we have combined cryo-electron tomographic studies of the 3D spatial architecture of chemoreceptor arrays in intact E. coli cells with computational modelling to develop a predictive model for the cooperativity and sensitivity of the chemotaxis response. The predictions were tested experimentally using fluorescence resonance energy transfer (FRET) microscopy. Our results demonstrate that changes in lateral packing densities of the partially ordered, spatially extended chemoreceptor arrays can modulate the bacterial chemotaxis response, and that information about the molecular organization of the arrays derived by cryo-electron tomography of intact cells can be translated into testable, predictive computational models of the chemotaxis response.
在趋化细菌中,跨膜化学感受器 CheA 和 CheW 形成了趋化感觉器官的核心信号复合物。这些复合物在细胞质膜中以扩展的阵列形式组织,使细菌能够通过协同变构反应对细胞外配体浓度的变化做出反应,从而导致配体结合诱导的信号显著放大。在这里,我们将完整的大肠杆菌细胞中趋化受体阵列的三维空间结构的低温电子断层扫描研究与计算建模相结合,为趋化反应的协同性和敏感性建立了一个预测模型。使用荧光共振能量转移(FRET)显微镜对预测结果进行了实验测试。我们的结果表明,部分有序的、空间扩展的趋化受体阵列的横向堆积密度的变化可以调节细菌的趋化反应,并且通过对完整细胞的低温电子断层扫描获得的关于阵列的分子组织的信息可以转化为可测试的、预测性的趋化反应计算模型。