CHAPTER 5: Iron–Sulfur Cluster-based Sensors

Iron–sulfur cluster proteins fulfil a wide range of functions in biology, the most recently discovered of which is as regulatory proteins that control the cellular response to a variety of environmental stimuli that cause intracellular changes. The inherent reactivity of iron–sulfur clusters, particularly towards small (gas) molecules, makes them ideal candidates to function as the sensory modules in such regulatory proteins. A wide range of data show that this is the case. Here, we review recent major advances in identifying and characterising iron–sulfur cluster regulators that sense O₂/oxidative stress, and NO/nitrosative stress. These include the first structures of the widespread O₂ sensor FNR and the NO sensor NsrR, and in vivo, biochemical, spectroscopic, kinetic and mass spectrometric data that provide new insight into how the iron–sulfur clusters of these proteins function in transducing the relevant signal to control the regulatory response.