5U8K

RitR mutant - C128S

Summary for 5U8K

• Entry DOI: 10.2210/pdb5u8k/pdb
• Related: 5U8M
• Descriptor: Response regulator (2 entities in total)
• Functional Keywords: repressor of iron transporter, aspartate-less receiver domain protein, transcription regulator, monomer, transcription
• Biological source: Streptococcus pneumoniae
• Total number of polymer chains: 2
• Total formula weight: 54876.61

Authors

Silvaggi, N.R.,Han, L. (deposition date: 2016-12-14, release date: 2017-12-20, Last modification date: 2024-10-23)

Primary citation

Glanville, D.G.,Han, L.,Maule, A.F.,Woodacre, A.,Thanki, D.,Abdullah, I.T.,Morrissey, J.A.,Clarke, T.B.,Yesilkaya, H.,Silvaggi, N.R.,Ulijasz, A.T.
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 Pathog., 14:e1007052-e1007052, 2018

PubMed 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 mechanism could be shared by many microbial species outside the streptococcus genus.

PubMed: 29750817
DOI: 10.1371/journal.ppat.1007052

Experimental method

X-RAY DIFFRACTION (1.69 Å)