Threonine phosphorylation prevents promoter DNA binding of the Group B Streptococcus response regulator CovR

Wan Jung Lin, Don Walthers, James E. Connelly, Kellie Burnside, Kelsea A. Jewell, Linda J. Kenney, Lakshmi Rajagopal

Research output: Contribution to journalArticlepeer-review

71 Scopus citations


All living organisms communicate with the external environment for their survival and existence. In prokaryotes, communication is achieved by two-component systems (TCS) comprising histidine kinases and response regulators. In eukaryotes, signalling is accomplished by serine/threonine and tyrosine kinases. Although TCS and serine/threonine kinases coexist in prokaryotes, direct cross-talk between these families was first described in Group B Streptococcus (GBS). A serine/threonine kinase (Stk1) and a TCS (CovR/CovS) co-regulate toxin expression in GBS. Typically, promoter binding of regulators like CovR is controlled by phosphorylation of the conserved active site aspartate (D53). In this study, we show that Stk1 phosphorylates CovR at threonine 65. The functional consequence of threonine phosphorylation of CovR in GBS was evaluated using phosphomimetic and silencing substitutions. GBS encoding the phosphomimetic T65E allele are deficient for CovR regulation unlike strains encoding the non-phosphorylated T65A allele. Further, compared with wild-type or T65A CovR, the T65E CovR is unable to bind promoter DNA and is decreased for phosphorylation at D53, similar to Stk1-phosphorylated CovR. Collectively, we provide evidence for a novel mechanism of response regulator control that enables GBS (and possibly other prokaryotes) to fine-tune gene expression for environmental adaptation.

Original languageEnglish (US)
Pages (from-to)1477-1495
Number of pages19
JournalMolecular Microbiology
Issue number6
StatePublished - Mar 2009
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology


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