Modelling of a metal-containing hepcidin |
| |
Authors: | Sebastien Farnaud Alpesh Patel Robert W Evans |
| |
Institution: | (1) Randall Division of Cell and Molecular Biophysics, King’s College London, Guy’s Hospital Campus, 3.6b New Hunt’s House, London, SE1 1UL, UK |
| |
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. |
| |
Keywords: | computer modelling hepcidin iron metabolism iron regulatory protein metallothionein |
本文献已被 SpringerLink 等数据库收录! |
|