Human calprotectin is an iron-sequestering host-defense protein
Name
Nolan_Human Calprotectin.pdf
Size
1.91 MB
Format
Adobe PDF
Checksum (MD5)
8d90a413d7f4b082975078281b0116ce
Author(s)
Zhang, Bo
Krebs, Carsten
Nakashige, Toshiki George
Nolan, Elizabeth Marie
Date Issued
August 2015
Journal
Nature Chemical Biology
Publisher
Springer Nature
Citation
Nakashige, Toshiki G., Bo Zhang, Carsten Krebs, and Elizabeth M. Nolan. “Human Calprotectin Is an Iron-Sequestering Host-Defense Protein.” Nat Chem Biol 11, no. 10 (August 24, 2015): 765–771.
Version
Author's final manuscript
Abstract
Human calprotectin (CP) is a metal-chelating antimicrobial protein of the innate immune response. The current working model states that CP sequesters manganese and zinc from pathogens. We report the discovery that CP chelates iron and deprives bacteria of this essential nutrient. Elemental analysis of CP-treated growth medium establishes that CP reduces the concentrations of manganese, iron and zinc. Microbial growth studies reveal that iron depletion by CP contributes to the growth inhibition of bacterial pathogens. Biochemical investigations demonstrate that CP coordinates Fe(II) at an unusual hexahistidine motif, and the Mössbauer spectrum of [superscript 57]Fe(II)-bound CP is consistent with coordination of high-spin Fe(II) at this site (δ = 1.20 mm/s, ΔE[subscript Q] = 1.78 mm/s). In the presence of Ca(II), CP turns on its iron-sequestering function and exhibits subpicomolar affinity for Fe(II). Our findings expand the biological coordination chemistry of iron and support a previously unappreciated role for CP in mammalian iron homeostasis.
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/10.1038/nchembio.1891
