1M4E

Solution Structure of Hepcidin-20

Summary for 1M4E

• Entry DOI: 10.2210/pdb1m4e/pdb
• Related: 1m4f
• NMR Information: BMRB: 5502
• Descriptor: Hepcidin (1 entity in total)
• Functional Keywords: strand-loop-strand, beta-sheet, hairpin loop, antimicrobial protein
• Cellular location: Secreted: P81172
• Total number of polymer chains: 1
• Total formula weight: 2203.83

Authors

Hunter, H.N.,Fulton, D.B.,Ganz, T.,Vogel, H.J. (deposition date: 2002-07-02, release date: 2002-11-06, Last modification date: 2024-10-16)

Primary citation

Hunter, H.N.,Fulton, D.B.,Ganz, T.,Vogel, H.J.
The solution structure of human hepcidin, a peptide hormone with antimicrobial activity that is involved in iron uptake and hereditary hemochromatosis.
J.Biol.Chem., 277:37597-37603, 2002

PubMed Abstract: The antibacterial and antifungal peptide hepcidin (LEAP-1) is expressed in the liver. This circulating peptide has recently been found to also act as a signaling molecule in iron metabolism. As such, it plays an important role in hereditary hemochromatosis, a serious iron overload disease. In this study, we report the solution structures of the hepcidin-20 and -25 amino acid peptides determined by standard two-dimensional (1)H NMR spectroscopy. These small cysteine-rich peptides form a distorted beta-sheet with an unusual vicinal disulfide bridge found at the turn of the hairpin, which is probably of functional significance. Both peptides exhibit an overall amphipathic structure with six of the eight Cys involved in maintaining interstrand connectivity. Hepcidin-25 assumes major and minor conformations centered about the Pro residue near the N-terminal end. Further NMR diffusion studies indicate that hepcidin-20 exists as a monomer in solution, whereas hepcidin-25 readily aggregates, a property that may contribute to the different activities of the two peptides. The nuclear Overhauser enhancement spectroscopy spectra of the hepcidin-25 aggregates indicate an interface for peptide interactions that again involves the first five residues from the N-terminal end.

PubMed: 12138110
DOI: 10.1074/jbc.M205305200

Experimental method

SOLUTION NMR