RitR is an archetype for a novel family of redox sensors in the streptococci that has evolved from two-component response regulators and is required for pneumococcal colonization

PLoS Pathogens
David G GlanvilleAndrew T Ulijasz

Abstract

To survive diverse host environments, the human pathogen Streptococcus pneumoniae must prevent its self-produced, extremely high levels of peroxide from reacting with intracellular iron. However, the regulatory mechanism(s) by which the pneumococcus accomplishes this balance remains largely enigmatic, as this pathogen and other related streptococci lack all known redox-sensing transcription factors. Here we describe a two-component-derived response regulator, RitR, as the archetype for a novel family of redox sensors in a subset of streptococcal species. We show that RitR works to both repress iron transport and enable nasopharyngeal colonization through a mechanism that exploits a single cysteine (Cys128) redox switch located within its linker domain. Biochemical experiments and phylogenetics reveal that RitR has diverged from the canonical two-component virulence regulator CovR to instead dimerize and bind DNA only upon Cys128 oxidation in air-rich environments. Atomic structures show that Cys128 oxidation initiates a "helical unravelling" of the RitR linker region, suggesting a mechanism by which the DNA-binding domain is then released to interact with its cognate regulatory DNA. Expanded computational studies indicate this ...Continue Reading

References

Apr 1, 1979·Journal of Bacteriology·J C LefevreA M Sicard
Jul 1, 1979·American Journal of Surgery·K P RammingD G Mulder
May 31, 1996·Journal of Molecular Biology·K MakinoM Suzuki
Jun 2, 2000·Science·J E Posey, F C Gherardini
Oct 27, 2001·Applied and Environmental Microbiology·C K SungD A Morrison
Jul 9, 2002·Molecular Microbiology·Skorn Mongkolsuk, John D Helmann
Dec 18, 2002·Journal of Bacteriology·Don WalthersLinda J Kenney
Jun 26, 2003·Nucleic Acids Research·Torsten SchwedeManuel C Peitsch
Jul 3, 2003·Journal of Bacteriology·Victoria L RobinsonAnn M Stock
Mar 5, 2004·The Lancet Infectious Diseases·D BogaertP W M Hermans
Oct 13, 2004·The Journal of Infectious Diseases·Carlos J OrihuelaElaine I Tuomanen
Nov 18, 2004·Journal of Bacteriology·Andrew T UlijaszBernard Weisblum
Sep 2, 2005·Molecular Microbiology·Stephen P KiddAlastair G McEwan
Mar 3, 2007·FEMS Microbiology Letters·Alexander HalfmannReinhold Brückner
Sep 12, 2007·Bioinformatics·M A LarkinD G Higgins
Oct 5, 2007·Current Opinion in Structural Biology·Hendrik SzurmantJames A Hoch
Nov 29, 2007·Molecular Cell·Kate J NewberryRichard G Brennan
Mar 15, 2008·Nature Reviews. Microbiology·Aras KadiogluPeter W Andrew
Jul 1, 2008·Journal of Bacteriology·Sumarin SoonsangaJohn D Helmann
Jul 9, 2008·Bioinformatics·Darren KessnerParag Mallick
Aug 9, 2008·The Journal of Biological Chemistry·Nirupama Gupta, Stephen W Ragsdale
Dec 17, 2008·Nature Chemical Biology·Daouda A K TraoréJean-Marc Latour
Feb 25, 2009·Acta Crystallographica. Section D, Biological Crystallography·Ludmila UrzhumtsevaAlexandre Urzhumtsev

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Citations

Jun 9, 2020·Frontiers in Cellular and Infection Microbiology·Lucia Gonzales-SilesMargarita Gomila
Mar 28, 2021·Journal of Applied Microbiology·P S Lannes-CostaP E Nagao
Sep 14, 2021·Journal of Bacteriology·Hemendra Pal Singh DhakedIndranil Biswas

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Methods Mentioned

BETA
immunoprecipitation
Size Exclusion Chromatography
X-ray
nuclear magnetic resonance
thermal shift
pulldown
PCR
Gel Filtration
NMR
immunoprecipitation assay

Software Mentioned

Python
MSConvert ( ProteoWizard : Open Source Software for Rapid Prot...
reduce
COOT
Swiss Model
Perl
pfam
MacBoxShade
autosol
Mascot

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