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PMID: 18680715 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Retracted Publication

The hepcidin-binding site on ferroportin is evolutionarily conserved.

Cell metabolism ·Vol. 8 ·No. 2 ·2008-08-00 ·Pages 146-56

De Domenico I, Nemeth E, Nelson JM, Phillips JD, Ajioka RS, Kay MS, Kushner JP, Ganz T, Ward DM, Kaplan J

Abstract

Mammalian iron homeostasis is regulated by the interaction of the liver-produced peptide hepcidin and its receptor, the iron transporter ferroportin. Hepcidin binds to ferroportin resulting in degradation of ferroportin and decreased cellular iron export. We identify the hepcidin-binding domain (HBD) on ferroportin and show that a synthetic 19 amino acid peptide corresponding to the HBD recapitulates the characteristics and specificity of hepcidin binding to cell-surface ferroportin. The binding of mammalian hepcidin to ferroportin or the HBD shows an unusual temperature dependency with an increased rate of dissociation at temperatures below 15 degrees C. The increased rate of dissociation is due to temperature- dependent changes in hepcidin structure. In contrast, hepcidin from poikilothermic vertebrates, such as fish or frogs, binds the HBD in a temperature-independent fashion. The affinity of hepcidin for the HBD permits a rapid, sensitive assay of hepcidin from all species and yields insights into the evolution of hepcidin.

MeSH Terms
Amino Acid Sequence/physiology Animals Antimicrobial Cationic Peptides/chemistry,metabolism Anura/metabolism Binding Sites/physiology Body Temperature/physiology Cation Transport Proteins/chemistry,metabolism Cell Line Conserved Sequence/physiology Evolution, Molecular Fishes/metabolism Hepcidins Humans Iron/metabolism Liver/metabolism Peptides/chemistry,metabolism Protein Structure, Tertiary/physiology Species Specificity
Chemicals
Antimicrobial Cationic Peptides Cation Transport Proteins HAMP protein, human Hepcidins Peptides metal transporting protein 1 Iron
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
De Domenico Ivana
Department of Pathology, School of Medicine, University of Utah, Salt Lake City, UT 84132, USA.
Nemeth Elizabeta
Nelson Jenifer M
Phillips John D
Ajioka Richard S
Kay Michael S
Kushner James P
Ganz Tomas
Ward Diane M
Kaplan Jerry
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Article Info
Journal
Cell metabolism
Abbr.
Cell Metab
ISSN
1932-7420
DOI
10.1016/j.cmet.2008.07.002
Published
2008-08-00
Pages
146-56
Language
English
Region
United States
NLM ID
101233170
PMCID
PMC2660598
Subset
IM
Grants
NIGMS NIH HHS · P50 GM082545 · United States
NIDDK NIH HHS · R01 DK070947-04 · United States
NIDDK NIH HHS · P30 DK072437 · United States
NIDDK NIH HHS · SP30DK072437 · United States
NIGMS NIH HHS · GM 082545 · United States
NIDDK NIH HHS · R01 DK070947 · United States
NIDDK NIH HHS · R01 DK020503 · United States
NIDDK NIH HHS · DK 070947 · United States
Corrections
CommentIn
PMID: 19245872
RetractionIn
PMID: 25025111
External Links
PubMed source DOI: 10.1016/j.cmet.2008.07.002 PMC Full Text View journal details
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