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. Circular dichroism spectroscopy of heme-based sensor proteins with distinct mechanisms of signal transduction, such as FixL and DevS, can be probed using a combination of regions of the spectrum (far-ultraviolet, near-ultraviolet, and particularly Soret regions), allowing also observations of minor to major changes within the heme domain. • Heme-based sensor proteins DevS and FixL were investigated from far-UV up to visible using circular dichroism. • Oxygen sensors with distinct mechanism of signal transduction can show distinct profiles for active versus inactive states. • CD of Soret band may provide a suitable hint of the role of propionate in signal transduction of heme-based sensors.
Guimarães et al. (Sun,) studied this question.