The FUR (ferric uptake regulator) superfamily: Diversity and versatility of key transcriptional regulators

•FUR proteins are a versatile family of regulators with a common structural fold.•Cross-talk between FUR proteins occurs in many bacteria.•Fur can work as activator and as repressor in both the apo and the metal-loaded forms.•Fur functionally interacts with many other regulators.•The potential role of Fur as a redox sensor deserves to be investigated.

Control of metal homeostasis is essential for life in all kingdoms. In most prokaryotic organisms the FUR (ferric uptake regulator) family of transcriptional regulators is involved in the regulation of iron and zinc metabolism through control by Fur and Zur proteins. A third member of this family, the peroxide-stress response PerR, is present in most Gram-positives, establishing a tight functional interaction with the global regulator Fur. These proteins play a pivotal role for microbial survival under adverse conditions and in the expression of virulence in most pathogens. In this paper we present the current state of the art in the knowledge of the FUR family, including those members only present in more reduced numbers of bacteria, namely Mur, Nur and Irr. The huge amount of work done in the two last decades shows that FUR proteins present considerable diversity in their regulatory mechanisms and interesting structural differences. However, much work needs to be done to obtain a more complete picture of this family, especially in connection with the roles of some members as gas and redox sensors as well as to fully characterize their participation in bacterial adaptative responses.