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Title: 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.
Authors: Glanville, David G.
Han, Lanlan
Maule, Andrew F.
Woodacre, Alexandra
Thanki, Devsaagar
Abdullah, Iman Tajer
Morrissey, Julie A.
Clarke, Thomas B.
Yesilkaya, Hasan
Silvaggi, Nicholas R.
Ulijasz, Andrew T.
First Published: 11-May-2018
Publisher: Public Library of Science
Citation: PLoS Pathogens, 2018, 14 (5), e1007052
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.
DOI Link: 10.1371/journal.ppat.1007052
ISSN: 1553-7366
eISSN: 1553-7374
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2018. This is an open-access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Description: All data underlying the findings described in this manuscript are freely available to other researchers, either in a public repository, or in the manuscript itself. Atomic structures have been deposited in RCSB protein databank under PBD codes 5U8K, 5VFA and 5U8M.
Appears in Collections:Published Articles, Dept. of Genetics

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