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dc.contributor.advisorVåbenø, Jon
dc.contributor.advisorClark, Richard
dc.contributor.advisoremailjon.våbenø@uit.noen
dc.contributor.advisoremailr.clark@imb.uq.edu.auen
dc.contributor.authorCarstens, Bodil Børte
dc.date.accessioned2009-10-19T07:20:38Z
dc.date.available2009-10-19T07:20:38Z
dc.date.issued2009-05-20
dc.description.abstractIron homeostasis is regulated by the interaction between the hormone hepcidin and the iron exporter ferroportin. Hepcidin is a cysteine-rich peptide which is secreted by hepatocytes in response to inflammation, eryhropoietic demand and iron stores. Hepcidin binds to its receptor ferroportin, inducing its internalisation and degradation, thus regulating the export of iron from cells to plasma. One of the aims of this study was to determine the three-dimensional (3D) structure of hepcidin using nuclear magnetic resonance (NMR) spectroscopy. The structure calculated consisted of a β-sheet with a hairpin loop showing a flexible N-terminus. The overall aim of this study was to analyse the interaction between hepcidin and ferroportin. Recently, mutational analysis revealed that hepcidin binds to a 20 residue extracellular loop on ferroportin, called the hepcidin-binding domain (HBD). Techniques including NMR spectroscopy, isothermal titration calorimetry (ITC), circular dichroism (CD) spectroscopy and surface plasmon resonance (SPR) spectroscopy were used. The results from all the assays performed indicate, however, that hepcidin does not bind to the HBD peptide. Three hepcidin analogues was synthesised to elucidate which residues in hepcidin that are important for the binding to ferroportin. The N-terminus of hepcidin is essential for binding to hepcidin and serial deletion of the N-terminal amino acids showed to cause progressive loss of activity when all five residues were deleted. Gly 20 was shown to have a key role in the interaction between hepcidin and ferroportin. This is the first mutation outside the N-terminus region that has activity.en
dc.format.extent1391954 bytes
dc.format.mimetypeapplication/pdf
dc.identifier.urihttp://hdl.handle.net/10037/2178
dc.identifier.urnURN:NBN:no-uit_munin_1930
dc.language.isoengen
dc.publisherUniversitetet i Tromsøen
dc.publisherUniversity of Tromsøen
dc.rights.accessRightsopenAccess
dc.subject.courseIDFAR-3901nor
dc.subjectVDP::Matematikk og naturvitenskap: 400::Kjemi: 440::Legemiddelkjemi: 448en
dc.titleThe analysis of the interaction between hepcidin and ferroportinen
dc.typeMastergradsoppgaveen
dc.typeMaster thesisen


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