The Solution Structure of Human Hepcidin, a Peptide Hormone with Antimicrobial Activity That Is Involved in Iron Uptake and Hereditary Hemochromatosis
Bibliographic record
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".