Circular dichroism: A possible route to shed light on signal transduction processes of heme-based gas-sensor proteins

Heme-based oxygen-sensor proteins differ in their signal transduction mechanisms. Nevertheless, they all rely directly on the ligation of oxygen to a heme cofactor in one domain to promote regulatory conformational changes in a responsive transmitter domain. DevS (also known as DosS) and FixL both represent cases where the heme-binding domain regulates a histidine protein kinase activity. On binding of oxygen, DevS changes its oligomeric state for signal transduction; this does not involve changes in the heme itself, but rather, the disruption of a hydrogen bonding network from the distal heme pocket toward the surface of the domain. By contrast, FixL remains dimeric but shows distortions of the porphyrin ring and changes in the orientations and contacts of the heme propionates that ultimately affect the kinase. In this study, we exploit circular dichroism (CD) in the far-UV, as well as the near-UV and the Soret regions, to investigate signal transduction signatures and relative thermal stability for DevS and FixL. Interestingly, the differences, as probed by CD, support active changes of the heme cofactor itself in the case of FixL, but not that of DevS. The study highlights the importance of CD as a tool with which to gain a broader spectroscopic window into signal transduction by heme-based sensors.