Do FeS clusters rule bacterial iron regulation?

For decades, the bacterial ferric uptake regulator (Fur) has been thought to respond to ferrous iron to transcriptionally regulate genes required for balancing iron uptake, storage, and utilization. Because iron binding to Fur has never been confirmed in vivo, the physiological iron-sensing mechanism remains an open question. Fontenot et al. now show that Fur purified from Escherichia coli binds an all-Cys-coordinated [2Fe-2S] cluster. This finding opens the exciting possibility that Fur may join numerous well-studied bacterial, fungal, and mammalian proteins that use FeS clusters for cellular iron regulation.