MOLECULAR STUDIES OF CHEMORECEPTION

活细胞的一个基本特征是能够对特定的， 外部化学信号 就像真核细胞对激素的反应一样 或神经递质，细菌含有特定的受体，暴露在 细胞表面，识别相关化合物。 这些细胞 趋化性是多组分作用的结果， 连接感受器和鞭毛的感觉反应系统。 长期 该实验室的目标是有助于详细的分子生物学 描述趋化系统。 最近的进展使它有可能 这将是第一个被详细了解的受体系统。 越来越多的细菌化学感受和 真核生物受体系统表明， 所获得的关于原核系统的信息将具有普遍意义。 该建议涉及生理学、遗传学和生物化学方法， 大肠杆菌化学感受性的研究。 主要重点是 放置在研究的传感器，这是一个完整的膜蛋白 对趋化性细胞的兴奋和适应阶段都很重要， 行为 适应包括转换器的共价修饰， 特别是在多个谷氨酰残基处蛋白质羧基甲基化 网站. 其中一些谷氨酰残基的存在是因为谷氨酰胺是 酶促脱酰胺以产生谷氨酸。 的功能意义 多重甲基化和脱酰胺化将通过改变 修饰位点使用合成的阿托伐他汀定向的 诱变 换能器低聚物的模式将用 希望能明确这些配合物在战术功能上的意义。 本文将介绍传感器的结构和构象变化 研究通过纯化蛋白质，通过使用光谱方法， 监测构象差异，并通过开发条件， 分子可以结晶。

A basic feature of living cells is the ability to respond to specific, external chemical signals. Like eukaryotic cells that respond to hormones or neurotransmitters, bacteria contain specific receptors, exposed on the cell surface, that recognize relevant compounds. These cells are chemotactic as the result of the functioning of a multicomponent, sensory-response system that links receptors to flagella. The long-term goal of this laboratory is to contribute to a detailed molecular biological description of the chemotactic system. Recent progress makes it likely that this will be the first receptor system to be understood in detail. The growing number of analogies between bacterial chemoreception and eukaryotic receptor systems suggest that at least some of the information obtained about the prokaryotic system will have general significance. This proposal involves physiological, genetic and biochemical approaches to the study of chemoreception in Escherichia coli. Primary emphasis is placed on the study of transducers, which are integral membrane proteins central to both the excitation and adaptation phases of chemotactic behavior. Adaptation involves covalent modification of transducers, specifically protein carboxyl methylation at multiple glutamyl residue sites. Some of those glutamyl residues are present because glutamines are enzymatically deamidated to create glutamates. The functional significance of multiple methylation and deamidation will be examined by alteration of the modification sites using synthetic oligonucleotide-directed mutagenesis. The pattern of transducer oligomers will be studied with the hope of defining the significance of these complexes in tactic function. The structure and conformational changes of transducers will be investigated by purifying the proteins, by using spectroscopic methods to monitor conformational differences and by developing conditions in which the molecules can be crystallized.