What a difference a cluster makes: The multifaceted roles of IscR in gene regulation and DNA recognition
2015
Santos, Joana A. | Pereira, Pedro José Barbosa | Macedo-Ribeiro, Sandra
Iron–sulfur clusters are essential cofactors in a myriad of metabolic pathways. Therefore, their biogenesis is tightly regulated across a variety of organisms and environmental conditions. In Gram-negative bacteria, two pathways – ISC and SUF – concur for maintaining intracellular iron–sulfur cluster balance. Recently, the mechanism of iron–sulfur cluster biosynthesis regulation by IscR, an iron–sulfur cluster-containing regulator encoded by the isc operon, was found to be conserved in some Gram-positive bacteria. Belonging to the Rrf2 family of transcriptional regulators, IscR displays a single helix-turn-helix DNA-binding domain but is able to recognize two distinct DNA sequence motifs, switching its specificity upon cluster ligation. This review provides an overview of gene regulation by iron–sulfur cluster-containing sensors, in the light of the recent structural characterization of cluster-less free and DNA-bound IscR, which provided insights into the molecular mechanism of nucleotide sequence recognition and discrimination of this unique transcription factor. This article is part of a Special Issue entitled: Cofactor-dependent proteins: evolution, chemical diversity and bio-applications.
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