This research elucidates adaptive responses in two similar but different systems. The first is the adaptation to sensory signals seen in bacterial chemotaxis, involving the aspartate receptor. The covalent modification of this receptor is being studied both by a combination of genetic engineering to modify the receptor and study its dynamic state, and by x-ray crystallographic techniques which are designed to understand the detailed protein structure. In addition, the feedback from the cytoplasmic constituents of the cellular system are explored in an attempt to understand the quantitative contribution of the cytoplasmic components relative to the contributions of the internal protein structure. The second adaptive system is the branch point operating at the isocitric dehydrogenase--isocitrate lyase position in Escherichia coli, which allows the bacteria to adapt to growth on varying levels of acetate, and other constituents. Studies focus on mutants of isocitric dehydrogenase and on recombinant DNA procedures which allow manipulation of the steps in the pathway in order to understand principles of regulatory control. The x- ray structure of the isocitric dehydrogenase will be determined to understand the role of mutants and the role of the induced conformational change in controlling the activity of the protein. Studies combining protein chemistry, enzyme kinetics and feedback control are leading to an understanding of adaptive behavior in model systems. Protein structure has been shown to be crucial for adaptation in microorganisms. This project is providing information on molecular mechanisms of adaptive responses.
