Atomic structures of chemotaxis receptors and complexes

描述(申请人提供)：细胞和有机体向或远离化学物质的移动，趋化性，是它们生存的关键行为，需要敏感信息检测和处理过程。细菌的趋化行为已经被深入研究了近40年，是人们最了解的信号转导系统之一。此外，使细菌能够以非凡的灵敏度和范围检测化学梯度的分子机制也可能在更复杂的生物体中发挥作用。 细菌趋化系统的单个组成蛋白有大量的信息，但一些最重要的关键信息缺乏，无法在原子水平上完全或接近完全地了解该系统的细胞过程的分子机制。缺少的关键信息之一是结构信息，如趋化受体及其复合体的三维原子结构。该方案的具体目的是获得野生型大肠杆菌趋化受体及其复合体以及锁定在信号开启或关闭状态的突变体受体的三维原子结构信息。 缺失的关键结构信息结合现有和未来的动态信息可能为定量理解趋化系统的细胞过程的分子机制、概念性地理解包括人类在内的高等生物中的信号系统以及导致针对细菌病原体的新的治疗方法奠定基础，其中许多细菌在感染过程中利用运动性和趋化性。

DESCRIPTION (provided by applicant): The movement of cells and organisms toward or away from chemicals, chemotaxis, is a crucial behavior for their survival that requires sensitive information detection and processing processes. Bacterial chemotactic behavior has been intensively studied for nearly 40 years and is one of the best understood signal transduction systems. Moreover, the molecular mechanisms that enable bacteria to detect chemical gradients with extraordinary sensitivity and range may operate also in more complex organisms. A large body of information is available for individual component proteins of bacterial chemotaxis systems, but some of the most important key information is missing for a complete or near-complete understanding of the molecular mechanisms of the cellular processes of the systems at an atomic level. One of the key missing information is structural information, such as 3-D atomic structures of chemotaxis receptors and their complexes. The specific aims of this proposal are to obtain the 3-D atomic structural information of wild type E. coli chemotaxis receptors and their complexes as well as mutant counterparts locked in signal on or off state. The missing key structural information combined with existing and future dynamic information may lay a foundation for quantitative understanding of molecular mechanisms of cellular processes of the chemotaxis system, for conceptual understanding of signaling systems in higher organisms including man, and for leading to new therapeutic approaches against bacterial pathogens, many of which employ motility and chemotaxis during the infection process.