title: Hepcidin revisited, disulfide connectivity, dynamics, and structure.
abstract: Hepcidin is a tightly folded 25-residue peptide hormone containing four disulfide bonds, which has been shown to act as the principal regulator of iron homeostasis in vertebrates. We used multiple techniques to demonstrate a disulfide bonding pattern for hepcidin different from that previously published. All techniques confirmed the following disulfide bond connectivity: Cys(1)-Cys(8), Cys(3)-Cys(6), Cys(2)-Cys(4), and Cys(5)-Cys(7). NMR studies reveal a new model for hepcidin that, at ambient temperatures, interconverts between two different conformations, which could be individually resolved by temperature variation. Using these methods, the solution structure of hepcidin was determined at 325 and 253 K in supercooled water. X-ray analysis of a co-crystal with Fab appeared to stabilize a hepcidin conformation similar to the high temperature NMR structure.
authors: Department of Molecular Structure, Amgen, Inc., Thousand Oaks, California 91320, USA. jbjordan@amgen.com
authors: John B
authors: JB
authors: Jordan
authors: Leszek
authors: L
authors: Poppe
authors: Mitsuru
authors: M
authors: Haniu
authors: Tara
authors: T
authors: Arvedson
authors: Rashid
authors: R
authors: Syed
authors: Vivian
authors: V
authors: Li
authors: Hiko
authors: H
authors: Kohno
authors: Helen
authors: H
authors: Kim
authors: Paul D
authors: PD
authors: Schnier
authors: Timothy S
authors: TS
authors: Harvey
authors: Les P
authors: LP
authors: Miranda
authors: Janet
authors: J
authors: Cheetham
authors: Barbra J
authors: BJ
authors: Sasu
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D018360:Crystallography, X-Ray; D004220:Disulfides / Q000737:chemistry* / Q000378:metabolism; D064451:Hepcidins; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D017510:Protein Folding; D017434:Protein Structure, Tertiary / Q000502:physiology
chemical_list: D023181:Antimicrobial Cationic Peptides; D004220:Disulfides; C578702:HAMP protein, human; D064451:Hepcidins