Hepcidin is a new peptide hormone secreted by the liver and widely distributed among animals, from fish to human. It acts as a signal molecule in iron metabolism and plays an important role in iron overload diseases. Recently, it has been reported that hepcidin is able to regulate the iron efflux by binding to the ferroportin protein and inducing its internalization. This activity is specific only for bioactive hepcidin-25 and not for the truncated hepcidin-20, lacking the five amino terminal residues. We have characterized the N-terminal region of the hepcidin-25 as a metal-binding site by several spectroscopic techniques and chemical studies. This region, specific for the coordination of Cu(II) and Ni(II), is known as 'ATCUN motif'. Moreover, we have demonstrated that the metal binding inhibits the aggregation propensity of both whole hepcidin-25 and its N-terminal fragments, probably inducing a conformational change leading to the stabilization of the N-terminal region. The identification of a metal-binding site at the N-terminus of hepcidin-25, which is necessary for its biological activity as iron-regulatory hormone, will help us to cast light both on the role of the divalent metals and of the hepcidin-25 in the iron homeostatis, and to better understand structure-function relationships of this hormone-peptide.
Melino, S., Garlando, L., Patamia, M., Paci, M., & Petruzzelli, R. (2005). A metal-binding site is present in the amino terminal region of the bioactive iron regulator hepcidin-25. JOURNAL OF PEPTIDE RESEARCH, 66, 65-71.
|Tipologia:||Articolo su rivista|
|Citazione:||Melino, S., Garlando, L., Patamia, M., Paci, M., & Petruzzelli, R. (2005). A metal-binding site is present in the amino terminal region of the bioactive iron regulator hepcidin-25. JOURNAL OF PEPTIDE RESEARCH, 66, 65-71.|
|IF:||Con Impact Factor ISI|
|Settore Scientifico Disciplinare:||Settore BIO/10|
|Revisione (peer review):||Sì, ma tipo non specificato|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1111/j.1747-0285.2006.00328.x|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||2005|
|Titolo:||A metal-binding site is present in the amino terminal region of the bioactive iron regulator hepcidin-25|
|Autori:||Melino, S ; Garlando, L ; Patamia, M ; Paci, M ; Petruzzelli, R|
|Appare nelle tipologie:||01 - Articolo su rivista|