AffiliationUniversity of Westminster
MetadataShow full item record
AbstractFollowing its identification as a liver-expressed antimicrobial peptide, the hepcidin peptide was later shown to be a key player in iron homoeostasis. It is now proposed to be the 'iron hormone' which, by interacting with the iron transporter ferroportin, prevents further iron import into the circulatory system. This conclusion was reached using the corresponding synthetic peptide, emphasizing the functional importance of the mature 25-mer peptide, but omitting the possible functionality of its maturation. From urine-purified native hepcidin, we recently demonstrated that a proportion of the purified hepcidin had formed iron-hepcidin complexes. This interaction was investigated further by computer modelling and, based on the sequence similarity of hepcidin with metallothionein, a three-dimensional model of hepcidin, containing one atom of iron, was constructed. To characterize these complexes further, the interaction with iron was analysed using different spectroscopic methods. Monoferric hepcidin was identified by MS, as were possibly other complexes containing two and three atoms of iron respectively, although these were present only in minor amounts. UV/visible absorbance and CD studies identified the iron-binding events which were facilitated at a physiological pH. EPR spectroscopy identified the ferric state of the bound metal, and indicated that the iron-hepcidin complex shares some similarities with the rubredoxin iron-sulfur complex, suggesting the presence of Fe(3+) in a tetrahedral sulfur co-ordination. The potential roles of iron binding for hepcidin are discussed, and we propose either a regulatory function in the maturation of pro-hepcidin into active hepcidin or as the necessary link in the interaction between hepcidin and ferroportin.
CitationFarnaud, S., et al (2008) 'Identification of an iron-hepcidin complex' Biochem. J. 413 (3):553-7
JournalThe Biochemical journal
- Modelling of a metal-containing hepcidin.
- Authors: Farnaud S, Patel A, Evans RW
- Issue date: 2006 Oct
- Iron regulatory and bactericidal properties of human recombinant hepcidin expressed in Pichia pastoris.
- Authors: Koliaraki V, Marinou M, Samiotaki M, Panayotou G, Pantopoulos K, Mamalaki A
- Issue date: 2008 May
- Recombinant human hepcidin expressed in Escherichia coli isolates as an iron containing protein.
- Authors: Gerardi G, Biasiotto G, Santambrogio P, Zanella I, Ingrassia R, Corrado M, Cavadini P, Derosas M, Levi S, Arosio P
- Issue date: 2005 Sep-Oct
- Quantification of hepcidin using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
- Authors: Bansal SS, Halket JM, Fusova J, Bomford A, Simpson RJ, Vasavda N, Thein SL, Hider RC
- Issue date: 2009 Jun
- The iron-regulatory peptide hormone hepcidin: expression and cellular localization in the mammalian kidney.
- Authors: Kulaksiz H, Theilig F, Bachmann S, Gehrke SG, Rost D, Janetzko A, Cetin Y, Stremmel W
- Issue date: 2005 Feb