Corynebacterium glutamicum WhcD interacts with WhiA to exert a regulatory effect on cell division genes

Lee, Dong‐Seok; Kim, Pil; Kim, Eung-Soo; Kim, Younhee; Lee, Heung-Shick

doi:10.1007/s10482-017-0953-0

Cited by 17 publications

(14 citation statements)

References 22 publications

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“…Despite the fact that WhiA is conserved in Gram-positive bacteria and is required for optimal growth in B. subtilis, surprisingly little is known about its mechanistic role. The only other organisms in which the function of WhiA has been studied are streptomycetes and C. glutamicum, and in these organisms, the protein functions as a transcription factor (4,5,19). In B. subtilis, WhiA also binds DNA, but the protein does not bind specifically to promoter regions and does not seem to function as a transcription factor in this organism (7).…”

Section: Discussionmentioning

confidence: 99%

“…Mutations in whiA prevent the induction of FtsZ and block sporulation (1)(2)(3)(4). WhiA binds DNA and functions as a transcription activator of ftsZ and other differentiation genes in Streptomyces spp., and recently, it has been shown to regulate ftsZ in Corynebacterium glutamicum as well (4,5).…”

Section: Importancementioning

confidence: 99%

“…subtilis WhiA binds DNA, but in contrast to streptomycetes and C. glutamicum WhiA, it does not influence the transcription of ftsZ or other cell division genes, and chromatin immunoprecipitation with microarray technology (ChIP-chip) experiments showed that the protein does not specifically bind to either promoter regions or a clear DNA consensus sequence (7). In streptomycetes and C. glutamicum, WhiA requires for its activity the auxiliary transcription factor WhiB (called WhcD in Corynebacterium) (5,18,19). However, homologues of these proteins are not present in B. subtilis.…”

Section: Importancementioning

confidence: 99%

See 2 more Smart Citations

The Conserved DNA Binding Protein WhiA Influences Chromosome Segregation in Bacillus subtilis

et al. 2018

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The DNA binding protein WhiA is conserved in Gram-positive bacteria and is present in the genetically simple cell wall-lacking mycoplasmas. The protein shows homology to eukaryotic homing endonucleases but lacks nuclease activity. WhiA was first characterized in streptomycetes, where it regulates the expression of key differentiation genes, including the cell division gene , which is essential for sporulation. For, it was shown that WhiA is essential when certain cell division genes are deleted. However, in , WhiA is not required for sporulation, and it does not seem to function as a transcription factor, despite its DNA binding activity. The exact function of WhiA remains elusive. We noticed that mutants show an increased space between their nucleoids, and here, we describe the results of fluorescence microscopy, genetic, and transcriptional experiments to further investigate this phenomenon. It appeared that the deletion of is synthetic lethal when either the DNA replication and segregation regulator ParB or the DNA replication inhibitor YabA is absent. However, WhiA does not seem to affect replication initiation. We found that a Δ mutant is highly sensitive for DNA-damaging agents. Further tests revealed that the deletion of induces the SOS response, including the cell division inhibitor YneA. When was inactivated, the viability of the synthetic lethal Δ Δ mutant was restored. However, the nucleoid segregation phenotype remained. These findings underline the importance of WhiA for cell division and indicate that the protein also plays a role in DNA segregation. The conserved WhiA protein family can be found in most Gram-positive bacteria, including the genetically simple cell wall-lacking mycoplasmas, and these proteins play a role in cell division. WhiA has some homology with eukaryotic homing endonucleases but lacks nuclease activity. Because of its DNA binding activity, it is assumed that the protein functions as a transcription factor, but this is not the case in the model system The function of this protein in remains unclear. We noticed that a mutant has a mild chromosome segregation defect. Further studies of this phenomenon provided new support for a functional role of WhiA in cell division and indicated that the protein is required for normal chromosome segregation.

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Section: Discussionmentioning

confidence: 99%

Section: Importancementioning

confidence: 99%

Section: Importancementioning

confidence: 99%

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The Conserved DNA Binding Protein WhiA Influences Chromosome Segregation in Bacillus subtilis

et al. 2018

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“…In Corynebacterium, the orthologue of WhiB, WhcD Cg , similarly regulates the transcription of genes required for cell division and directly interacts with the orthologue of WhiA in vitro (Lee et al , ; ) . WhcD Cg cannot bind to promoter DNA by itself but stimulates the binding of WhiA to the ftsZ promoter, suggesting that WhcD enhances the DNA‐binding activity of WhiA through protein–protein interaction (Lee et al , ).…”

Section: Class II (Whib2/whib/whcd)mentioning

confidence: 99%

The actinobacterial WhiB‐like (Wbl) family of transcription factors

Bush

2018

Molecular Microbiology

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SummaryThe WhiB‐like (Wbl) family of proteins are exclusively found in Actinobacteria. Wbls have been shown to play key roles in virulence and antibiotic resistance in Mycobacteria and Corynebacteria, reflecting their importance during infection by the human pathogens Mycobacterium tuberculosis, Mycobacterium leprae and Corynebacterium diphtheriae. In the antibiotic‐producing Streptomyces, several Wbls have important roles in the regulation of morphological differentiation, including WhiB, a protein that controls the initiation of sporulation septation and the founding member of the Wbl family. In recent years, genome sequencing has revealed the prevalence of Wbl paralogues in species throughout the Actinobacteria. Wbl proteins are small (generally ~80–140 residues) and each contains four invariant cysteine residues that bind an O2‐ and NO‐sensitive [4Fe–4S] cluster, raising the question as to how they can maintain distinct cellular functions within a given species. Despite their discovery over 25 years ago, the Wbl protein family has largely remained enigmatic. Here I summarise recent research in Mycobacteria, Corynebacteria and Streptomyces that sheds light on the biochemical function of Wbls as transcription factors and as potential sensors of O2 and NO. I suggest that Wbl evolution has created diversity in protein–protein interactions, [4Fe–4S] cluster‐sensitivity and the ability to bind DNA.

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“…The interaction of Wbl proteins with other proteins is also known; work in both Streptomyces and Corynebacterium revealed that WhiB controls the process of sporulation via a direct interaction with a (non-Wbl) transcription factor called WhiA (5,16). Thus, evidence is accumulating that Wbl proteins function together with partner proteins.…”

mentioning

confidence: 99%

Interaction of the Streptomyces Wbl protein WhiD with the principal sigma factor σHrdB depends on the WhiD [4Fe-4S] cluster

Stewart

Bush

Crack

et al. 2020

Journal of Biological Chemistry

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The bacterial protein WhiD belongs to the Wbl family of iron-sulfur [Fe-S] proteins present only in the actinomycetes. In Streptomyces coelicolor, it is required for the late stages of sporulation, but precisely how it functions is unknown. Here, we report results from in vitro and in vivo experiments with WhiD from Streptomyces venezuelae (SvWhiD), which differs from S. coelicolor WhiD (ScWhiD) only at the C terminus. We observed that, like ScWhiD and other Wbl proteins, SvWhiD binds a [4Fe-4S] cluster that is moderately sensitive to O2 and highly sensitive to nitric oxide (NO). However, although all previous studies have reported that Wbl proteins are monomers, we found that SvWhiD exists in a monomer-dimer equilibrium associated with its unusual C-terminal extension. Several Wbl proteins of Mycobacterium tuberculosis are known to interact with its principal sigma factor SigA. Using bacterial two-hybrid, gel filtration, and MS analyses, we demonstrate that SvWhiD interacts with domain 4 of the principal sigma factor of Streptomyces, σHrdB (σHrdB4). Using MS, we determined the dissociation constant (Kd) for the SvWhiD-σHrdB4 complex as ∼0.7 μm, consistent with a relatively tight binding interaction. We found that complex formation was cluster dependent and that a reaction with NO, which was complete at 8–10 NO molecules per cluster, resulted in dissociation into the separate proteins. The SvWhiD [4Fe-4S] cluster was significantly less sensitive to reaction with O2 and NO when SvWhiD was bound to σHrdB4, consistent with protection of the cluster in the complex.

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Corynebacterium glutamicum WhcD interacts with WhiA to exert a regulatory effect on cell division genes

Cited by 17 publications

References 22 publications

The Conserved DNA Binding Protein WhiA Influences Chromosome Segregation in Bacillus subtilis

The Conserved DNA Binding Protein WhiA Influences Chromosome Segregation in Bacillus subtilis

The actinobacterial WhiB‐like (Wbl) family of transcription factors

Interaction of the Streptomyces Wbl protein WhiD with the principal sigma factor σHrdB depends on the WhiD [4Fe-4S] cluster

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