Characterization of the bacterial Arc system.

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DESCRIPTION (provided by applicant) The Arc two-component signal transduction system of Escherichia coil modulates the expression of numerous operons according to the redox condition of growth. This system comprises ArcB as the sensor kinase and ArcA as the response regulator. Under reducing conditions, dimeric ArcB undergoes ATP-dependent autophosphorylation and catalyzes the phosphorylation of ArcA by a His-Asp-His-Asp phosphorelay. Phosphorylated ArcA represses transcription of numerous operons involved in aerobic respiration and activates a small number of operons involved in fermentation. D-lactate, pyruvate, and acetate stimulate ArcB autophosphorylation. Under oxidizing conditions, the accumulating ubiquinone or menaquinone inhibits ArcB autophosphorylation, thereby allowing ArcB to catalyze net dephosphorylation of ArcA-P via an Asp-His-Asp reverse relay. Characterization of the Arc system will deepen our understanding of how bacteria optimize their strategy for energy metabolism.The proposed project has three main aims. The first is to locate the quinone reception site in ArcB and define the mode of action of the signal. The second is to determine which phosphotransfer step in signal transmission and signal decay occurs intermolecularly between the two subunits of ArcB. The last objective is to explore the true role of the cytosolic PAS domain in ArcB, erroneously reported to be the receptor site for the redox signal.This research will be done primarily in Mexico as an extension of NIH grant #R01 GM40993.