Understanding the structure/activity relationships of the iron regulatory peptide hepcidin

Clark, Richard J., Tan, Chia Chia, Preza, Gloria C., Nemeth, Elizabeta, Ganz, Tomas and Craik, David J. (2011) Understanding the structure/activity relationships of the iron regulatory peptide hepcidin. Chemistry and Biology, 18 3: 336-343. doi:10.1016/j.chembiol.2010.12.009


Author Clark, Richard J.
Tan, Chia Chia
Preza, Gloria C.
Nemeth, Elizabeta
Ganz, Tomas
Craik, David J.
Title Understanding the structure/activity relationships of the iron regulatory peptide hepcidin
Journal name Chemistry and Biology   Check publisher's open access policy
ISSN 1074-5521
1879-1301
Publication date 2011-03
Sub-type Article (original research)
DOI 10.1016/j.chembiol.2010.12.009
Volume 18
Issue 3
Start page 336
End page 343
Total pages 8
Place of publication Cambridge, MA, U.S.A.
Publisher Cell Press
Collection year 2012
Language eng
Formatted abstract
The peptide hormone hepcidin is a key homeostatic regulator of iron metabolism and involved in pathological regulation of iron in response to infection, inflammation, hypoxia, and anemia. It acts by binding to the iron exporter ferroportin, causing it to be internalized and degraded; however, little is known about the structure/activity relationships of the interaction of hepcidin with ferroportin. We show that there are key residues in the N-terminal region of hepcidin that influence its interaction with ferroportin, and we explore the structure/function relationships at these positions. A series of hepcidin mutants in which disulfide bonds were replaced with diselenide bonds showed no change in activity compared to native hepcidin. These results identify important constraints for the development of hepcidin congeners for the treatment of hereditary iron overload.

Highlights: ► Identified key residues in hepcidin N terminus for binding to ferroportin ► Explored the structure/activity relationships at each of these key positions ► Explored the role of the disulfide bonds in the interaction between hepcidin and ferroportin
Keyword Hereditary hemochromatosis
Antimicrobial activity
Molecular-basis
HFE
Ferroportin
Homeostasis
Mutations
Chemistry
Proteins
HAMP
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
Institute for Molecular Bioscience - Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 21 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 20 Sep 2011, 12:25:41 EST by Dr Richard Clark on behalf of Institute for Molecular Bioscience