Characterization of the PAS domain in the sensor-kinase BvgS: mechanical role in signal transmission

We propose that a major function of the BvgS PAS domain is to maintain conformational signals arising from mechanical strain generated by the periplasmic domain. The tight structure of the PAS core and its connections with the upstream and downstream helices ensure signaling to the kinase domain, which determines BvgS activity. Many mild substitutions that map to the PAS domain keep BvgS active but make it unresponsive to negative modulators, supporting that modulation increases conformational strain in the protein.