title: Copper(II) binding properties of hepcidin.
abstract: 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.
authors.affiliation: Faculty of Pharmacy, Payap University, Mae Khao Campus, Chiang Mai, Thailand.
authors.forename: Kanokwan
authors.initials: K
authors.lastname: Kulprachakarn
authors.affiliation: Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK.
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK.
authors.forename: Xiaole
authors.initials: X
authors.lastname: Kong
authors.affiliation: Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Arno
authors.affiliation: Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Hider
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
authors.forename: Somdet
authors.initials: S
authors.lastname: Srichairatanakool
authors.affiliation: Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK. sukhi.bansal@kcl.ac.uk.
authors.forename: Sukhvinder S
authors.initials: SS
authors.lastname: Bansal
mesh_terms: D003300:Copper / Q000737:chemistry*; D064451:Hepcidins / Q000138:chemical synthesis / Q000737:chemistry; D013058:Mass Spectrometry; D011199:Potentiometry
chemical_list: D064451:Hepcidins; D003300:Copper
keywords: Binding affinity; Biomedicine; Homeostasis; Mass spectrometry; Peptide