Human calprotectin affects the redox speciation of iron
Name
nihms881420.pdf
Size
1.02 MB
Format
Adobe PDF
Checksum (MD5)
83e4a5bccfaa4956ca8737763b085f8e
Author(s)
Nakashige, Toshiki George
Nolan, Elizabeth Marie
Date Issued
May 2017
Journal
Metallomics
Publisher
Royal Society of Chemistry (RSC)
Citation
Nakashige, Toshiki G., and Elizabeth M. Nolan. “Human Calprotectin Affects the Redox Speciation of Iron.” Metallomics 9, 8 (2017): 1086–1095 © 2017 The Royal Society of Chemistry
Version
Author's final manuscript
Abstract
We report that the metal-sequestering human host-defense protein calprotectin (CP, S100A8/S100A9 oligomer) affects the redox speciation of iron (Fe) in bacterial growth media and buffered aqueous solution. Under aerobic conditions and in the absence of an exogenous reducing agent, CP-Ser (S100A8(C42S)/S100A9(C3S) oligomer) depletes Fe from three different bacterial growth media preparations over a 48 h timeframe (T = 30 °C). The presence of the reducing agent β-mercaptoethanol accelerates this process and allows CP-Ser to deplete Fe over a ≈1 h timeframe. Fe-depletion assays performed with metal-binding-site variants of CP-Ser show that the hexahistidine (His6) site, which coordinates Fe(ii) with high affinity, is required for Fe depletion. An analysis of Fe redox speciation in buffer containing Fe(iii) citrate performed under aerobic conditions demonstrates that CP-Ser causes a time-dependent increase in the [Fe(ii)]/[Fe(iii)] ratio. Taken together, these results indicate that the hexahistidine site of CP stabilizes Fe(ii) and thereby shifts the redox equilibrium of Fe to the reduced ferrous state under aerobic conditions. We also report that the presence of bacterial metabolites affects the Fe-depleting activity of CP-Ser. Supplementation of bacterial growth media with an Fe(iii)-scavenging siderophore (enterobactin, staphyloferrin B, or desferrioxamine B) attenuates the Fe-depleting activity of CP-Ser. This result indicates that formation of Fe(iii)-siderophore complexes blocks CP-mediated reduction of Fe(iii) and hence the ability of CP to coordinate Fe(ii). In contrast, the presence of pyocyanin (PYO), a redox-cycling phenazine produced by Pseudomonas aeruginosa that reduces Fe(iii) to Fe(ii), accelerates Fe depletion by CP-Ser under aerobic conditions. These findings indicate that the presence of microbial metabolites that contribute to metal homeostasis at the host/pathogen interface can affect the metal-sequestering function of CP.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1039/C7MT00044H
