Organization of the E. coli receptor signaling complex

描述（由申请人提供）：趋化细菌在广泛的浓度范围内具有高灵敏度的化学梯度。本研究的目的是阐明大肠杆菌化学受体信号复合物的功能结构。该复合物由跨膜受体蛋白组成，与组氨酸激酶CheA和偶联蛋白CheW协同作用，将化学刺激放大为胞质信号，控制细胞运动。为了确定CheW和CheA如何与受体信号域相互作用，我建议分离在这些相互作用中有特异性缺陷的受体突变体，使用一系列遗传和生化测试来确定所需的突变体。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（具有两个共价连接亚基的分子）来研究，以控制高阶受体复合物中的亚基组成和几何形状。由于趋化性和趋化受体与许多类型细菌的发病机制有关，这些研究应该为趋化受体的分子信号策略提供一般知识，并可能为毒力机制提供有价值的新见解。

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.