Recognition of DNA by Fur: a Reinterpretation of the Fur Box Consensus Sequence
Noel Baichoo,John D. Helmann +1 more
TLDR
By envisioning a similar mode of DNA recognition for Fur, this work can account for the internal symmetries noted previously within the Fur box, the tendency of Fur to extend into adjacent regions of DNA in a sequence-selective manner, and the observed patterns of DNA protection against enzymatic and chemical probes.Abstract:
Ferric uptake repressor (Fur) proteins regulate the expression of iron homeostasis genes in response to intracellular iron levels. In general, Fur proteins bind with high affinity to a 19-bp inverted repeat sequence known as the Fur box. An alignment of 19 operator sites recognized by Bacillus subtilis Fur revealed a different conserved 15-bp (7-1-7) inverted repeat present twice within this 19-bp consensus sequence. We demonstrated using electrophoretic mobility shift assays that this 7-1-7 inverted repeat comprises a minimal recognition site for high-affinity binding by Fur. The resulting revised consensus sequence is remarkably similar to a related 7-1-7 inverted repeat sequence recognized by PerR, a Fur paralog. Our analysis of the affinity and stoichiometry of DNA binding by B. subtilis Fur, together with a reinterpretation of previously described studies of Escherichia coli Fur, supports a model in which the 19-bp Fur box represents overlapping recognition sites for two Fur dimers bound to opposite faces of the DNA helix. The resulting recognition complex is reminiscent of that observed for the functionally related protein DtxR. Like Fur, DtxR contains a helix-turn-helix DNA-binding motif, recognizes a 19-bp inverted repeat sequence, and has a typical DNase I footprint of ∼30 bp. By envisioning a similar mode of DNA recognition for Fur, we can account for the internal symmetries noted previously within the Fur box, the tendency of Fur to extend into adjacent regions of DNA in a sequence-selective manner, and the observed patterns of DNA protection against enzymatic and chemical probes.read more
Citations
More filters
Journal ArticleDOI
Bacterial iron homeostasis
TL;DR: The expression of the iron homeostatic machinery is subject to iron-dependent global control ensuring that iron acquisition, storage and consumption are geared to iron availability and that intracellular levels of free iron do not reach toxic levels.
Journal ArticleDOI
Bacterial Iron Sources: From Siderophores to Hemophores
TL;DR: Recent genetic, biochemical, and crystallographic studies have allowed substantial progress in describing molecular mechanisms of siderophore and hemophore interactions with the outer membrane receptors, transport through the inner membrane, iron storage, and regulation of genes encoding biosynthesis and uptake proteins.
Journal ArticleDOI
Effect of RyhB Small RNA on Global Iron Use in Escherichia coli
TL;DR: The results demonstrate the broad effects of a single noncoding RNA on iron homeostasis and observe repression of Fur-regulated genes upon RyhB expression, interpreted as due to intracellular iron sparing resulting from reduced synthesis of iron-binding proteins.
Journal ArticleDOI
Functional specialization within the Fur family of metalloregulators
Jin-Won Lee,John D. Helmann +1 more
TL;DR: There is a tremendous diversity in metal selectivity and biological function within the Fur family which includes sensors of iron (Fur), zinc (Zur), manganese (Mur), and nickel (Nur), and the mechanism of metal ion sensing by Fur family proteins is still controversial.
Journal ArticleDOI
At the Crossroads of Bacterial Metabolism and Virulence Factor Synthesis in Staphylococci
TL;DR: This review uses information derived primarily using Bacillus subtilis and Escherichia coli to articulate how gram-positive pathogens, with emphasis on Staphylococcus aureus and Staphyllococcus epidermidis, regulate virulence determinant expression in response to a changing environment.
References
More filters
Journal ArticleDOI
Opening the Iron Box: Transcriptional Metalloregulation by the Fur Protein
TL;DR: It is generally accepted that iron is the most important micronutrient used by bacteria, but this element is not easily available to microorganisms in aerobic environments, so iron uptake has to be exquisitely regulated to maintain the intracellular concentration of the metal between desirable limits.
Journal ArticleDOI
DNA Recognition by Proteins with the Helix-Turn-Helix Motif
TL;DR: In this article, the authors discuss the importance of recognizing the HTH to DNA and the role of the Antp Homeodomain in the identification of the origin of DNA.
Journal ArticleDOI
Operator sequences of the aerobactin operon of plasmid ColV-K30 binding the ferric uptake regulation (fur) repressor.
TL;DR: The promoter region of the pColV-K30-encoded operon specifying biosynthesis and transport of the siderophore aerobactin was subjected to deletion analysis to determine the smallest DNA sequence affording iron regulation of a iucA'-'lacZ gene fusion.
Journal ArticleDOI
Bacillus subtilis contains multiple Fur homologues: identification of the iron uptake (Fur) and peroxide regulon (PerR) repressors
TL;DR: It is demonstrated that a ygaG mutant has the perR phenotype: it is highly resistant to peroxides and overexpresses catalase, alkyl hydroperoxide reductase and the DNA binding protein MrgA, and it encodes the peroxide regulon repressor and is allelic with perR.
Journal ArticleDOI
Identification of a Zinc-Specific Metalloregulatory Protein, Zur, Controlling Zinc Transport Operons in Bacillus subtilis
Ahmed Gaballa,John D. Helmann +1 more
TL;DR: It is concluded that Zur is a Fur-like repressor that controls the expression of two zinc homeostasis operons in response to zinc, which means Fur- like regulators control zincHomeostasis in addition to their previously characterized roles in regulating iron homeostatic responses, acid tolerance responses, and oxidative stress functions.