Organization of the E. coli receptor signaling complex

大肠杆菌受体信号复合物的组织

• 批准号: 6836176
• 负责人: PATRICIA A MOWERY
• 金额: $ 4.11万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6836176
• 关键词: Escherichia coli; SDS polyacrylamide gel electrophoresis; bacterial proteins; biological signal transduction; chemoreceptors; chemotaxis; histidine; mutant; polymerase chain reaction; postdoctoral investigator; protein kinase; protein protein interaction; protein purification; protein structure function; receptor binding; receptor coupling; serine; site directed mutagenesis

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.

描述（由申请人提供）：趋化细菌在很宽的浓度范围内以高灵敏度感知化学梯度。本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，这些蛋白与组氨酸激酶 CheA 和偶联蛋白 CheW 协同工作，将化学刺激放大为控制细胞运动的细胞质信号。为了确定 CheW 和 CheA 如何与受体信号传导域相互作用，我建议使用一系列遗传和生化测试来识别所需的突变体，从而分离在这些相互作用中存在特定缺陷的受体突变体。将通过使用单链受体（具有两个共价连接的亚基的分子）来研究 CheA 和 CheW 在受体信号传导团队中的位置，以控制高阶受体复合物中的亚基组成和几何形状。这些研究应该提供化学感受器分子信号传导策略的一般知识，并可能为毒力机制提供有价值的新见解，因为趋化性和化学感受器与许多类型细菌的发病机制相关。