Copper(II) binding properties of hepcidin

摘要

Hepcidin is a peptide hormone that regulates the homeostasis of iron metabolism. The N-terminal domain of hepcidin is conserved amongst a range of species and is capable of binding Cu-II and Ni-II through the amino terminal copper-nickel binding motif (ATCUN). It has been suggested that the binding of copper to hepcidin may have biological relevance. In this study we have investigated the binding of Cu-II with model peptides containing the ATCUN motif, fluorescently labelled hepcidin and hepcidin using MALDI-TOF mass spectrometry. As with albumin, it was found that tetrapeptide models of hepcidin possessed a higher affinity for Cu-II than that of native hepcidin. The log K (1) value of hepcidin for Cu-II was determined as 7.7. Cu-II binds to albumin more tightly than hepcidin (log K (1) = 12) and in view of the serum concentration difference of albumin and hepcidin, the bulk of kinetically labile Cu-II present in blood will be bound to albumin. It is estimated that the concentration of Cu-II-hepcidin will be less than one femtomolar in normal serum and thus the binding of copper to hepcidin is unlikely to play a role in iron homeostasis. As with albumin, small tri and tetra peptides are poor models for the metal binding properties of hepcidin.