ArticlePloS one2013
New insights into histidine triad proteins: solution structure of a Streptococcus pneumoniae PhtD domain and zinc transfer to AdcAII.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 52 citations in OpenAlex.
- Higher levels of mucosal antibody to pneumococcal vaccine candidate proteins are associated with reduced acute otitis media caused by Streptococcus pneumoniae in young children.Mucosal immunology · 2015Trial
- The Slr protein of Streptococcus pyogenes is selectively expressed in vivo and is a target for protective antibodies.EMBO molecular medicine · 2026Article
- The global proteome ofFrontiers in cellular and infection microbiology · 2025Article
- Review
- The AdcACB/AdcAII system is essential for zinc homeostasis and an important contributor ofVirulence · 2022Article
- Nutritional immunity: the battle for nutrient metals at the host-pathogen interface.Nature reviews. Microbiology · 2022Review
- In silico designing of a novel epitope-based candidate vaccine against Streptococcus pneumoniae with introduction of a new domain of PepO as adjuvant.Journal of translational medicine · 2022Article
- Zinc import mediated by AdcABC is critical for colonization of the dental biofilm by Streptococcus mutans in an animal model.Molecular oral microbiology · 2021Article
- Broadly Reactive Human Monoclonal Antibodies Targeting the Pneumococcal Histidine Triad Protein Protect against Fatal Pneumococcal Infection.Infection and immunity · 2021Article
- Asterix/Gtsf1 links tRNAs and piRNA silencing of retrotransposons.Cell reports · 2021Article
- Conformation of the Solute-Binding Protein AdcAII Influences Zinc Uptake inFrontiers in cellular and infection microbiology · 2021Article
- How Zinc-Binding Systems, Expressed by Human Pathogens, Acquire Zinc from the Colonized Host Environment: A Critical Review on Zincophores.Current medicinal chemistry · 2021Review
- Inactivation of theVirulence · 2020Article
- Structural Features Mediating Zinc Binding and Transfer in the AztABCD Zinc Transporter System.Biomolecules · 2020Article
- Group A Streptococcus AdcR Regulon Participates in Bacterial Defense against Host-Mediated Zinc Sequestration and Contributes to Virulence.Infection and immunity · 2020Article
- Manganese Depletion Leads to Multisystem Changes in the Transcriptome of the Opportunistic PathogenFrontiers in microbiology · 2020Article
- Defining the Role of theJournal of bacteriology · 2019Article
- Two ABC Transporters and a Periplasmic Metallochaperone Participate in Zinc Acquisition in Paracoccus denitrificans.Biochemistry · 2019Article
- Crystal structures of AztD provide mechanistic insights into direct zinc transfer between proteins.Communications biology · 2019Article
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6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Zinc (Zn(2+)) homeostasis is critical for pathogen host colonization and invasion. Polyhistidine triad (Pht) proteins, located at the surface of various streptococci, have been proposed to be involved in Zn(2+) homeostasis. The phtD gene, coding for a Zn(2+)-binding protein, is organized in an operon with adcAII coding for the extracellular part of a Zn(2+) transporter. In the present work, we investigate the relationship between PhtD and AdcAII using biochemical and structural biology approaches. Immuno-precipitation experiments on purified membranes of Streptococcus pneumoniae (S. pneumoniae) demonstrate that native PhtD and AdcAII interact in vivo confirming our previous in vitro observations. NMR was used to demonstrate Zn(2+) transfer from the Zn(2+)-bound form of a 137 amino acid N-terminal domain of PhtD (t-PhtD) to AdcAII. The high resolution NMR structure of t-PhtD shows that Zn(2+) is bound in a tetrahedral site by histidines 83, 86, and 88 as well as by glutamate 63. Comparison of the NMR parameters measured for apo- and Zn(2+)-t-PhtD shows that the loss of Zn(2+) leads to a diminished helical propensity at the C-terminus and increases the local dynamics and overall molecular volume. Structural comparison with the crystal structure of a 55-long fragment of PhtA suggests that Pht proteins are built from short repetitive units formed by three β-strands containing the conserved HxxHxH motif. Taken together, these results support a role for S. pneumoniae PhtD as a Zn(2+) scavenger for later release to the surface transporter AdcAII, leading to Zn(2+) uptake.
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