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.