MOLECULAR EVENTS IN A DISCRETE CYTOPLASMIC SPACE

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DESCRIPTION (provided by applicant): In this project, a small and specialized volume of cytoplasm associated with a cluster of chemotactic receptors on the surface of the bacterium Escherichia coli will be analyzed in great detail, using computer modeling, stochastic simulation techniques, and a novel 3D prototyping technique. Models of the receptors and associated proteins, at atomic resolution, will be assembled into a two-dimensional lattice resembling the cluster of receptors in the bacterial membrane in an arrangement consistent with biochemical, kinetic, mutational and behavioral data. The cytoplasmic domains of the receptors will then be used to define a small volume of cytoplasm subjacent to the plasma membrane and to examine the concentrations, distributions and diffusive behavior of "soluble" enzymes that interact with the receptors in the course of adaptation. The feasibility of a two-handed, "brachiation" motion of enzymes through the lattice, due to their possession of two relatively weak binding sites for the receptors will be examined. We will also explore the theoretical possibility that conformational changes might spread, from one receptor to its neighbors in the lattice via intervening proteins, and thereby lead to the emergence of large-scale coherent patterns of activity. The results of this study are likely to provide novel insight not only on bacterial chemotaxis but also, more generally, on other membrane-associated protein complexes, such as focal adhesions in fibroblasts and postsynaptic densities in the vertebrate central nervous system.