Regulation of streptokinase expression by CovR/S in Streptococcus pyogenes: CovR acts through a single high-affinity binding site.
The important human pathogen Streptococcus pyogenes (the group A streptococcus or GAS) produces many virulence factors that are regulated by the two-component signal transduction system CovRS (CsrRS). Dissemination of GAS infection originating at the skin has been shown to require production of streptokinase, whose transcription is repressed by CovR. In this work we have studied the interaction of CovR and phosphorylated CovR (CovR-P) with the promoter for streptokinase, Pska. We found that, in contrast to the other CovR-repressed promoters, Pska regulation by CovR occurs through binding at a single ATTARA consensus binding sequence (CB) that overlaps the -10 region of the promoter. Binding of CovR to other nearby consensus sequences occurs upon phosphorylation of the protein, but these other CBs do not contribute to the regulation of Pska by CovR. Thus, binding at a specific site does not necessarily indicate that the site is involved in regulation by CovR. In addition, at Pska, CovR binding to the different sites does not appear to involve cooperative interactions, which simplifies the analysis of CovR binding and gives us insight into the modes of interaction that occur between CovR and its specific DNA-binding sites. Finally, the observation that regulation of transcription from Pska occurs at a very low concentration of phosphorylated CovR may have important implications for the regulation of virulence gene expression during GAS infection.
Churchward
Gordon
G
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Bates
Christopher
C
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Gusa
Asiya A
AA
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Stringer
Virginia
V
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Scott
June R
JR
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D000071677:Histidine Kinase; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013297:Streptococcus pyogenes / Q000737:chemistry / Q000201:enzymology / Q000235:genetics*; D013300:Streptokinase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D001426:Bacterial Proteins; C432143:CsrR protein, Streptococcus pyogenes; D047908:Intracellular Signaling Peptides and Proteins; D012097:Repressor Proteins; C534547:CovS protein, Streptococcus pyogenes; D000071677:Histidine Kinase; D013300:Streptokinase