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Crystal structures of SlyA protein, a master virulence regulator of Salmonella, in free and DNA-bound states.

ABSTRACT: SlyA is a master virulence regulator that controls the transcription of numerous genes in Salmonella enterica. We present here crystal structures of SlyA by itself and bound to a high-affinity DNA operator sequence in the slyA gene. SlyA interacts with DNA through direct recognition of a guanine base by Arg-65, as well as interactions between conserved Arg-86 and the minor groove and a large network of non-base-specific contacts with the sugar phosphate backbone. Our structures, together with an unpublished structure of SlyA bound to the small molecule effector salicylate (Protein Data Bank code 3DEU), reveal that, unlike many other MarR family proteins, SlyA dissociates from DNA without large conformational changes when bound to this effector. We propose that SlyA and other MarR global regulators rely more on indirect readout of DNA sequence to exert control over many genes, in contrast to proteins (such as OhrR) that recognize a single operator.

SUBMITTER: Dolan KT

PROVIDER: S-EPMC3121362 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Crystal structures of SlyA protein, a master virulence regulator of Salmonella, in free and DNA-bound states.

Dolan Kyle T KT Duguid Erica M EM He Chuan C

The Journal of biological chemistry 20110505 25

SlyA is a master virulence regulator that controls the transcription of numerous genes in Salmonella enterica. We present here crystal structures of SlyA by itself and bound to a high-affinity DNA operator sequence in the slyA gene. SlyA interacts with DNA through direct recognition of a guanine base by Arg-65, as well as interactions between conserved Arg-86 and the minor groove and a large network of non-base-specific contacts with the sugar phosphate backbone. Our structures, together with an ...[more]

PMID: 21550983

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Project description:AtxA, the master virulence regulator of Bacillus anthracis, regulates the expression of three toxins and genes for capsule formation that are required for the pathogenicity of B. anthracis. Recent transcriptome analyses showed that AtxA affects a large number of genes on the chromosome and plasmids, suggesting a role as a global regulator. However, information on genes directly regulated by AtxA is scarce. In this work, we conducted genome-wide analyses and cataloged the binding sites of AtxA in vivo and transcription start sites on the B. anthracis genome. By integrating these results, we detected eight genes as direct regulons of AtxA. These consisted of five protein-coding genes, including two of the three toxin genes, and three genes encoding the small RNAs XrrA and XrrB and a newly discovered 95-nucleotide small RNA, XrrC. Transcriptomes from single-knockout mutants of these small RNAs revealed changes in the transcription levels of genes related to the aerobic electron transport chain, heme biosynthesis, and amino acid metabolism, suggesting their function for the control of cell physiology. These results reveal the first layer of the gene regulatory network for the pathogenicity of B. anthracis and provide a data set for the further study of the genomics and genetics of B. anthracis. IMPORTANCE Bacillus anthracis is the Gram-positive bacterial species that causes anthrax. Anthrax is still prevalent in countries mainly in Asia and Africa, where it causes economic damage and remains a public health issue. The mechanism of pathogenicity is mainly explained by the three toxin proteins expressed from the pXO1 plasmid and by proteins involved in capsule formation expressed from the pXO2 plasmid. AtxA is a protein expressed from the pXO1 plasmid that is known to upregulate genes involved in toxin production and capsule formation and is thus considered the master virulence regulator of B. anthracis. Therefore, understanding the detailed mechanism of gene regulation is important for the control of anthrax. The significance of this work lies in the identification of genes that are directly regulated by AtxA via genome-wide analyses. The results reveal the first layer of the gene regulatory network for the pathogenicity of B. anthracis and provide useful resources for a further understanding of B. anthracis.

Dataset Information

Crystal structures of SlyA protein, a master virulence regulator of Salmonella, in free and DNA-bound states.

Publications

Crystal structures of SlyA protein, a master virulence regulator of Salmonella, in free and DNA-bound states.

Similar Datasets

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