The Pneumococcal Iron Uptake Protein A (PiuA) Specifically Recognizes Tetradentate FeIIIbis- and Mono-Catechol Complexes
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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier BV
2020
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| Online Access: | https://hdl.handle.net/1721.1/128018 |
| _version_ | 1826210092229328896 |
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| author | Zhang, Yifan Edmonds, Katherine A. Raines, Daniel J. Murphy, Brennan A. Wu, Hongwei Guo, Chuchu Nolan, Elizabeth Marie VanNieuwenhze, Michael S. Duhme-Klair, Anne-K. Giedroc, David P. |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Zhang, Yifan Edmonds, Katherine A. Raines, Daniel J. Murphy, Brennan A. Wu, Hongwei Guo, Chuchu Nolan, Elizabeth Marie VanNieuwenhze, Michael S. Duhme-Klair, Anne-K. Giedroc, David P. |
| author_sort | Zhang, Yifan |
| collection | MIT |
| description | 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 an 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. |
| first_indexed | 2024-09-23T14:42:38Z |
| format | Article |
| id | mit-1721.1/128018 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:42:38Z |
| publishDate | 2020 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1280182022-10-01T22:09:07Z The Pneumococcal Iron Uptake Protein A (PiuA) Specifically Recognizes Tetradentate FeIIIbis- and Mono-Catechol Complexes Zhang, Yifan Edmonds, Katherine A. Raines, Daniel J. Murphy, Brennan A. Wu, Hongwei Guo, Chuchu Nolan, Elizabeth Marie VanNieuwenhze, Michael S. Duhme-Klair, Anne-K. Giedroc, David P. Massachusetts Institute of Technology. Department of Chemistry 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 an 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. 2020-10-16T14:45:14Z 2020-10-16T14:45:14Z 2020-09 2020-08 2020-10-05T13:35:43Z Article http://purl.org/eprint/type/JournalArticle 0022-2836 https://hdl.handle.net/1721.1/128018 Zhang, Yifan et al. "The Pneumococcal Iron Uptake Protein A (PiuA) Specifically Recognizes Tetradentate FeIIIbis- and Mono-Catechol Complexes." Journal of Molecular Biology 432, 19 (September 2020): 5390-5410 © 2020 Elsevier Ltd en http://dx.doi.org/10.1016/j.jmb.2020.08.005 Journal of Molecular Biology Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf application/pdf Elsevier BV Prof. Nolan via Ye Li |
| spellingShingle | Zhang, Yifan Edmonds, Katherine A. Raines, Daniel J. Murphy, Brennan A. Wu, Hongwei Guo, Chuchu Nolan, Elizabeth Marie VanNieuwenhze, Michael S. Duhme-Klair, Anne-K. Giedroc, David P. The Pneumococcal Iron Uptake Protein A (PiuA) Specifically Recognizes Tetradentate FeIIIbis- and Mono-Catechol Complexes |
| title | The Pneumococcal Iron Uptake Protein A (PiuA) Specifically Recognizes Tetradentate FeIIIbis- and Mono-Catechol Complexes |
| title_full | The Pneumococcal Iron Uptake Protein A (PiuA) Specifically Recognizes Tetradentate FeIIIbis- and Mono-Catechol Complexes |
| title_fullStr | The Pneumococcal Iron Uptake Protein A (PiuA) Specifically Recognizes Tetradentate FeIIIbis- and Mono-Catechol Complexes |
| title_full_unstemmed | The Pneumococcal Iron Uptake Protein A (PiuA) Specifically Recognizes Tetradentate FeIIIbis- and Mono-Catechol Complexes |
| title_short | The Pneumococcal Iron Uptake Protein A (PiuA) Specifically Recognizes Tetradentate FeIIIbis- and Mono-Catechol Complexes |
| title_sort | pneumococcal iron uptake protein a piua specifically recognizes tetradentate feiiibis and mono catechol complexes |
| url | https://hdl.handle.net/1721.1/128018 |
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