Regulatory control of the Streptococcus mutans HdrRM LytTR Regulatory System functions via a membrane sequestration mechanism

Zhoujie Xie, Zhengzhong Zou, Assaf Raz, Hua Qin, Vincent Fischetti, Shan Zhang, Jens Kreth, Justin Merritt

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Bacteria sense and respond to environmental changes via several broad categories of sensory signal transduction systems. Recently, we described the key features of a previously unrecognized, but widely conserved class of prokaryotic sensory system that we refer to as the LytTR Regulatory System (LRS). Our previous studies suggest that most, if not all, prokaryotic LRS membrane proteins serve as inhibitors of their cognate transcription regulators, but the inhibitory mechanisms employed have thus far remained a mystery. Using the Streptococcus mutans HdrRM LRS as a model, we demonstrate how the LRS membrane protein HdrM inhibits its cognate transcription regulator HdrR by tightly sequestering HdrR in a membrane-localized heteromeric HdrR/M complex. Membrane sequestration of HdrR prevents the positive feedback autoregulatory function of HdrR, thereby maintaining a low basal expression of the hdrRM operon. However, this mechanism can be antagonized by ectopically expressing a competitive inhibitor mutant form of HdrR that lacks its DNA binding ability while still retaining its HdrM interaction. Our results indicate that sequestration of HdrR is likely to be the only mechanism required to inhibit its transcription regulator function, suggesting that endogenous activation of the HdrRM LRS is probably achieved through a modulation of the HdrR/M interaction.

Original languageEnglish (US)
Pages (from-to)681-693
Number of pages13
JournalMolecular Microbiology
Issue number4
StatePublished - Oct 1 2020


  • ECF sigma factor
  • LytTR regulatory system
  • Streptococcus mutans
  • sequestration
  • signal transduction
  • two-component signal transduction system

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology


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