Iron–sulfur cluster sensor-regulators

Regulatory proteins that contain an iron–sulfur cluster cofactor constitute a group that is growing both in number and importance, with a range of functions that include sensing of molecular oxygen, stress response, and iron regulation. In all cases, the cluster plays a central role, as a sensory module, in controlling the activity of the regulator. In some cases, the cluster is required for the protein to attain its regulatory form, while in others the active form requires loss or modification of the cluster. In this way, nature has exploited the inherent reactivity of iron–sulfur clusters. Here, we focus on recent advances that provide new insight into the remarkable chemistries exhibited by these regulators, and how they achieve the required levels of sensitivity and specificity.

► Evolutionary tuning of the reactivity and specificity of iron–sulfur clusters.
► The mechanism of nitrosylation of iron–sulfur clusters involved in nitric oxide sensing.
► Redox sensing by iron–sulfur clusters: the SoxR paradigm.
► Differential regulation by Rrf2 family iron–sulfur cluster regulators in different forms.