2.50
Hdl Handle:
http://hdl.handle.net/10547/593392
Title:
Identification of an iron-hepcidin complex
Authors:
Farnaud, Sébastien; Rapisarda, Chiara; Bui, Tam; Drake, Alex; Cammack, Richard; Evans, Robert W
Abstract:
Following 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.
Affiliation:
University of Westminster
Citation:
Farnaud, S., et al (2008) 'Identification of an iron-hepcidin complex' Biochem. J. 413 (3):553-7
Publisher:
Portland Press
Journal:
The Biochemical journal
Issue Date:
1-Aug-2008
URI:
http://hdl.handle.net/10547/593392
DOI:
10.1042/BJ20080406
PubMed ID:
18447830
Additional Links:
http://www.biochemj.org/content/413/3/553.long
Type:
Article
Language:
en
ISSN:
1470-8728
Appears in Collections:
Cell and Cryobiology Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorFarnaud, Sébastienen
dc.contributor.authorRapisarda, Chiaraen
dc.contributor.authorBui, Tamen
dc.contributor.authorDrake, Alexen
dc.contributor.authorCammack, Richarden
dc.contributor.authorEvans, Robert Wen
dc.date.accessioned2016-01-14T12:26:15Zen
dc.date.available2016-01-14T12:26:15Zen
dc.date.issued2008-08-01en
dc.identifier.citationFarnaud, S., et al (2008) 'Identification of an iron-hepcidin complex' Biochem. J. 413 (3):553-7en
dc.identifier.issn1470-8728en
dc.identifier.pmid18447830en
dc.identifier.doi10.1042/BJ20080406en
dc.identifier.urihttp://hdl.handle.net/10547/593392en
dc.description.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.en
dc.language.isoenen
dc.publisherPortland Pressen
dc.relation.urlhttp://www.biochemj.org/content/413/3/553.longen
dc.rightsArchived with thanks to The Biochemical journalen
dc.subjecthepcidinsen
dc.subjectiron chemistryen
dc.subject.meshAntimicrobial Cationic Peptidesen
dc.subject.meshCircular Dichroismen
dc.subject.meshElectron Spin Resonance Spectroscopyen
dc.subject.meshHepcidinsen
dc.subject.meshIronen
dc.subject.meshProtein Bindingen
dc.subject.meshProtonsen
dc.subject.meshSpectrometry, Mass, Matrix-Assisted Laser Desorption-Ionizationen
dc.titleIdentification of an iron-hepcidin complexen
dc.typeArticleen
dc.contributor.departmentUniversity of Westminsteren
dc.identifier.journalThe Biochemical journalen

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