Hepcidin Revisited, Disulfide Connectivity, Dynamics, and Structure

Hepcidin Revisited, Disulfide Connectivity, Dynamics, and Structure

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 publi...

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Bibliographic Details
Published in:The Journal of biological chemistry Vol. 284; no. 36; pp. 24155 - 24167
Main Authors: Jordan, John B., Poppe, Leszek, Haniu, Mitsuru, Arvedson, Tara, Syed, Rashid, Li, Vivian, Kohno, Hiko, Kim, Helen, Schnier, Paul D., Harvey, Timothy S., Miranda, Les P., Cheetham, Janet, Sasu, Barbra J.
Format: Journal Article
Language:English
Published: United States Elsevier Inc 04-09-2009
American Society for Biochemistry and Molecular Biology
Subjects:
Animals
Antimicrobial Cationic Peptides - chemistry
Antimicrobial Cationic Peptides - genetics
Antimicrobial Cationic Peptides - metabolism
CHO Cells
Cricetinae
Cricetulus
Crystallography, X-Ray
Disulfides - chemistry
Disulfides - metabolism
Hepcidins
Humans
Nuclear Magnetic Resonance, Biomolecular
Protein Folding
Protein Structure and Folding
Protein Structure, Tertiary - physiology
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Summary: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: Cys1–Cys8, Cys3–Cys6, Cys2–Cys4, and Cys5–Cys7. 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.
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ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M109.017764