Regulatory control of the Streptococcus mutans HdrRM LytTR Regulatory System functions via a membrane sequestration mechanism
Year: 2020
Type: article
Abstract: 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.
Source: Molecular Microbiology
DOI: 10.1111/mmi.14576
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: Oregon Health and Science University, Rockefeller University, National Institutes of Health, National Eye Institute, National Cancer Institute, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Center for Research Resources
Awards: G1235228070, G1581679921, G1935934802, G2161670674, G2162071218, LTQ XL Linear Ion Trap Mass Spectrometer, G2466695617, G2517144053, G2535433541, A Novel Class of Signal Transduction System in Streptococcus mutans, G3952897278, G4374229610, Pyruvate oxidase determines ecological fitness of oral streptococci, Pyruvate oxidase determines ecological fitness of oral streptococci, G8216061809, G8373157242, G8899923248, Hair Bundle Proteins, Ophthalmology Core Facility, OHSU Knight Cancer Institute, G908311096
OpenAlex ID: W3045337454