title: Understanding the structure/activity relationships of the iron regulatory peptide hepcidin.
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.
authors: The University of Queensland, Institute for Molecular Bioscience, Brisbane, Queensland 4072, Australia. richard.clark@uq.edu.au
authors: Richard J
authors: RJ
authors: Clark
authors: Chia Chia
authors: CC
authors: Tan
authors: Gloria C
authors: GC
authors: Preza
authors: Elizabeta
authors: E
authors: Nemeth
authors: Tomas
authors: T
authors: Ganz
authors: David J
authors: DJ
authors: Craik
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000737:chemistry / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry; D064451:Hepcidins; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000628:therapy; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012643:Selenium / Q000737:chemistry; D013329:Structure-Activity Relationship; D000098742:Ferroportin
chemical_list: D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; D004220:Disulfides; C578702:HAMP protein, human; D064451:Hepcidins; D000098742:Ferroportin; D007501:Iron; D012643:Selenium