Zhang, Yifan, Edmonds, Katherine A, Raines, Daniel J orcid.org/0000-0002-3015-6327 et al. (7 more authors) (2020) The Pneumococcal Iron Uptake Protein a (PiuA) Specifically Recognizes Tetradentate FeIIIbis- and Mono-Catechol Complexes. Journal of Molecular Biology. ISSN 0022-2836
Abstract
Streptococcus pneumoniae (Spn) is an important Gram-positive human pathogen that causes millions of infections worldwide with an increasing occurrence of antibiotic resistance. Fe acquisition is a crucial virulence determinant in Spn; further, Spn relies on exogenous FeIII-siderophore scavenging to meet nutritional Fe needs. Recent studies suggest that the human catecholamine stress hormone, norepinephrine (NE), facilitates Fe acquisition in Spn under conditions of transferrin-mediated Fe starvation. Here we show that the solute binding lipoprotein PiuA from the piu Fe acquisition ABC transporter PiuBCDA, previously described as an Fe-hemin binding protein, binds tetradentate catechol FeIII complexes, including NE and the hydrolysis products of enterobactin. Two protein-derived ligands (H238, Y300) create a coordinately-saturated FeIII complex, which parallel recent studies in the Gram-negative intestinal pathogen Campylobacter jejuni. Our in vitro studies using NMR spectroscopy and 54Fe LC-ICP-MS confirm the FeIII can move from transferrin to apo-PiuA in a NE-dependent manner. Structural analysis of PiuA FeIII-bis-catechol and GaIII-bis-catechol and GaIII-(NE)2 complexes by NMR spectroscopy reveals only localized structural perturbations in PiuA upon ligand binding, largely consistent with recent descriptions of other solute binding proteins of type II ABC transporters. We speculate that tetradentate FeIII complexes formed by mono- and bis-catechol species are important Fe sources in Gram-positive human pathogens, since PiuA functions in the same way as SstD from Staphylococcus aureus.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details. |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) |
Funding Information: | Funder Grant number EPSRC EP/L024829/1 UNSPECIFIED EP/T007338/1 |
Depositing User: | Pure (York) |
Date Deposited: | 25 Aug 2020 16:40 |
Last Modified: | 22 Dec 2024 00:14 |
Published Version: | https://doi.org/10.1016/j.jmb.2020.08.005 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1016/j.jmb.2020.08.005 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:164831 |
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