Modelling of a metal-containing hepcidin

Sebastien Farnaud, Alpesh Patel, Robert W. Evans

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Hepcidin was originally identified as a liver-expressed antimicrobial peptide but further studies have shown that it also has a key role in iron homeostasis. The NMR structure of the synthetic peptides reveal a distorted beta-sheet containing 4 disulphide bridges, with an unusual vicinal disulphide bridge which has been suggested to be functionally significant. In this study, we report the presence of co-purified iron with the urine-purified 20 and 25 residue hepcidins. Since the published structure does not allow metal binding, the interaction of hepcidin with metals was investigated for other possible structural conformations by threading its primary sequence onto existing 3D folds. Several alignments were obtained and the best scores were used to build a 3D model of hepcidin containing one atom of iron. The new 3D structure, that contains only reduced Cys residues, is completely different from the solved structure of the synthetic peptide. Although the model presented here shows only one metal bound to the peptide, the binding of several metal atoms cannot be excluded from such a short flexible peptide. The co-purification of iron with both peptides, together with our 3D model, suggest a conformational polymorphism for hepcidin, reminiscent of the iron regulatory proteins IRPs.

Original languageEnglish
Pages (from-to)527-533
Number of pages7
JournalBioMetals
Volume19
Issue number5
DOIs
Publication statusPublished - Oct 2006
Externally publishedYes

Keywords

  • Computer modelling
  • Hepcidin
  • Iron metabolism
  • Iron regulatory protein
  • Metallothionein

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Modelling of a metal-containing hepcidin'. Together they form a unique fingerprint.

Cite this