title: Human calprotectin is an iron-sequestering host-defense protein.
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 (57)Fe(II)-bound CP is consistent with coordination of high-spin Fe(II) at this site (δ = 1.20 mm/s, ΔEQ = 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.
authors: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors: Toshiki G
authors: TG
authors: Nakashige
authors: Department of Chemistry, Pennsylvania State University, University Park, Pennsylvania, USA.
authors: Bo
authors: B
authors: Zhang
authors: Department of Chemistry, Pennsylvania State University, University Park, Pennsylvania, USA.|Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania, USA.
authors: Carsten
authors: C
authors: Krebs
authors: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors: Elizabeth M
authors: EM
authors: Nolan
mesh_terms: D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D054884:Host-Pathogen Interactions / Q000502:physiology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000378:metabolism / Q000494:pharmacology*; D048191:Lactiplantibacillus plantarum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D039841:Leukocyte L1 Antigen Complex / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D008826:Microbial Sensitivity Tests; D015204:Spectroscopy, Mossbauer; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*
chemical_list: D007502:Iron Chelating Agents; D039841:Leukocyte L1 Antigen Complex; D007501:Iron; D002118:Calcium