In a paper published in the Dec. 16 issue of the Proceedings of the National Academy of Sciences (USA) researchers from the Gardner laboratory and the UT Southwestern Structural Biology Lab describe their studies of a novel light-activated histidine kinase. Such enzymes commonly serve as the environmental sensors for bacteria via their roles in “two component signaling pathways,” sensitizing their hosts to a wide range of stimuli. The vast majority of these enzymes are dimers, requiring the association of two copies of the same protein to function properly. Notably, this dimeric nature is central to most of the models of signaling among these proteins, which often postulate that environmental changes trigger the movement of one subunit by the other in motions like scissors, pistons or other devices.
Here, the Gardner lab combined several structural biology methods – including X-ray diffraction, NMR spectroscopy and limited proteolysis – to investigate a new monomeric histidine kinase that works without requiring a dimeric partner. Building on a foundation of structural studies of other light-sensing proteins, it was discovered that this protein (“EL346”) functions by the direct binding of sensory and regulatory components to each other. In doing so, light-induced structural changes can be more directly transmitted through the protein. These findings suggest novel routes for additional bacterial factors to control histidine kinase activity, and further, for the design of novel environmentally-sensitive proteins for biotechnology applications.