title: What a difference a cluster makes: The multifaceted roles of IscR in gene regulation and DNA recognition.
abstract: 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.
authors: IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal.
authors: Joana A
authors: JA
authors: Santos
authors: IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal. Electronic address: ppereira@ibmc.up.pt.
authors: Pedro José Barbosa
authors: PJ
authors: Pereira
authors: IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal. Electronic address: sribeiro@ibmc.up.pt.
authors: Sandra
authors: S
authors: Macedo-Ribeiro
mesh_terms: D000595:Amino Acid Sequence; D004269:DNA, Bacterial / Q000378:metabolism*; D004926:Escherichia coli; D029968:Escherichia coli Proteins / Q000502:physiology*; D015964:Gene Expression Regulation, Bacterial; D054884:Host-Pathogen Interactions; D008969:Molecular Sequence Data; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; C499695:IscR protein, E coli; D014157:Transcription Factors
keywords: Iron–sulfur cluster biogenesis; Protein–DNA interaction; Rrf2 family; Transcription regulation