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Characterization of the transition-metal-binding properties of hepcidin
- Source :
- The Biochemical journal. 427(2)
- Publication Year :
- 2010
-
Abstract
- Accumulating evidence suggests that hepcidin, a 25-residue peptide hormone, is the master regulator of iron metabolism. Further evidence suggests that the five N-terminal amino acids are crucial for mediating its biological function. With a histidine residue at position 3, this region also has the potential to bind bivalent metal ions. To characterize this hepcidin–metal interaction in detail, the present study utilizes electrospray MS to measure the binding of a range of metal ions to wild-type and mutant human and murine hepcidins. In addition, the biological effects of these point mutations were tested on Caco-2 and HEK-293T human cell lines and in mice. Our results show that hepcidin-25 can form complexes with copper, nickel and zinc; however, we failed to detect any hepcidin-25 binding to either ferric or ferrous ions. The greatest affinity observed was between hepcidin-25 and copper with a dissociation constant ≪1 μM. Substituting the histidine residue at position 3 in human hepcidin-25 and comparably the asparagine residue at position 3 in murine hepcidin-25 with an alanine residue markedly diminished the affinity for copper. The amino acid substitutions also decreased the biological activity of hepcidin-25; namely repression of ferroportin protein levels and hypoferraemia. In summary, the high affinity of hepcidin for copper suggests that hepcidin could bind copper in vivo and this may be of biological relevance.
- Subjects :
- inorganic chemicals
congenital, hereditary, and neonatal diseases and abnormalities
Spectrometry, Mass, Electrospray Ionization
Cations, Divalent
Ferroportin
Plasma protein binding
digestive system
Biochemistry
Cell Line
Mice
Hepcidins
Hepcidin
hemic and lymphatic diseases
Metals, Heavy
Transition Elements
Animals
Humans
Point Mutation
Asparagine
Molecular Biology
Alanine
chemistry.chemical_classification
biology
Chemistry
nutritional and metabolic diseases
Biological activity
Cell Biology
Amino acid
Dissociation constant
Amino Acid Substitution
biology.protein
Copper
Antimicrobial Cationic Peptides
Protein Binding
Subjects
Details
- ISSN :
- 14708728
- Volume :
- 427
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- The Biochemical journal
- Accession number :
- edsair.doi.dedup.....e1edbf7840fd50aa6d843426c32d13f4