Organization of the E. coli receptor signaling complex

描述（由申请方提供）：趋化性细菌在宽浓度范围内以高灵敏度感知化学梯度。该研究的目的是阐明大肠杆菌化学感受器信号复合物的功能结构。该复合物由跨膜受体蛋白组成，这些跨膜受体蛋白与组氨酸激酶CheA和偶联蛋白CheW合作，将化学刺激放大为控制细胞运动的细胞质信号。为了确定如何咀嚼和CheA与受体信号传导结构域相互作用，我建议隔离受体突变体，特别是在这些相互作用的缺陷，使用一系列的遗传和生化测试，以确定所需的突变体。CheA和CheW在受体信号传导团队中的位置将通过使用单链受体-具有两个共价连接的亚基的分子-来控制高阶受体复合物中的亚基组成和几何形状来研究。这些研究应该提供化学感受器的分子信号转导策略的一般知识和可能有价值的新见解的毒力机制，以及，因为趋化性和化学感受器与致病机制在许多类型的细菌。

DESCRIPTION (provided by applicant): Chemotactic bacteria sense chemical gradients with high sensitivity over a wide concentration range. The goal of the proposed research is to elucidate the functional architecture of the chemoreceptor signaling complex of Escherichia coli. The complex is composed of transmembrane receptor proteins that operate in cooperative teams with a histidine kinase, CheA, and a coupling protein, CheW, to amplify chemical stimuli into cytoplasmic signals that control cell motility. To determine how CheW and CheA interact with the receptor signaling domains, I propose to isolate receptor mutants that are specifically defective in those interactions, using a series of genetic and biochemical tests to identify the desired mutants. The locations of CheA and CheW in receptor signaling teams will be investigated by using single-chain receptors - molecules with two covalently connected subunits - to control the subunit composition and geometry in higher-order receptor complexes. These studies should provide general knowledge of the molecular signaling strategies of chemoreceptors and possibly valuable new insights into virulence mechanisms, as well, because chemotaxis and chemoreceptors are associated with pathogenesis in many types of bacteria.