Bacteria use two-component systems (TCSs) to transduce signals across a lipid membrane. In Gram negative bacteria, the PhoPQ TCS confers virulence and is activated in the absence of Mg2+, at low pH, or in the presence of antimicrobial peptides. While this response is well known, the structural rearrangements required to transmit these signals remain contested. This dimeric sensor histidine kinase (PhoQ) has multiple helical bundle domains that a signal must pass through to obtain a genetic response. Previously, we utilized disulfide-scanning and Bayesian inference to construct a model of PhoQ signal transduction. We described helical rearrangements associated with signaling. Here, we study PhoQ mutants by in vivo activity assays along with in vitro hydrogen/deuterium exchange studies to pinpoint the residues that are critical in this signaling cascade. These mutational scans highlight the importance of structural integrity within a particular domain as well as critical tertiary interactions between domains.

Mutational analysis of the PhoQ signal transduction pathway

248th National Meeting (2014)

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