Abstract
The murine 10-residue neurohormone kisspeptin (YNWNSFGLRY) is an important regulator of reproductive behavior and gonadotrophin secretion. It is known to form a random coil in solution, but undergoes a structural change in the presence of membranes although the nature of this change is not fully determined. The peptide's conformational versatility raises the question whether it is also able to form ordered aggregates under physiological conditions, which might be relevant as a storage mechanism. Here we show that heparin induces kisspeptin to form beta-sheet rich amyloid aggregates both at neutral (pH 7.0) and slightly acidic (pH 5.2) conditions. Addition of heparin leads to aggregation after a certain lag phase, irrespective of the time of addition of heparin, indicating that heparin is needed to facilitate the formation of fibrillation nuclei. Aggregation is completely inhibited by submicellar concentrations of zwitterionic and anionic surfactants. Unlike previous reports, our NMR data do not indicate persistent structure in the presence of zwitterionic surfactant micelles. Thus kisspeptin can aggregate under physiologically relevant conditions provided heparin is present, but the process is highly sensitive to the presence of amphiphiles, highlighting the very dynamic nature of the peptide conformation and suggesting that kisspeptin aggregation is a biologically regulatable process.
| Original language | English |
|---|---|
| Journal | Biopolymers |
| Volume | 93 |
| Issue | 8 |
| Pages (from-to) | 678-89 |
| Number of pages | 12 |
| ISSN | 0006-3525 |
| DOIs | |
| Publication status | Published - 1 Aug 2010 |
Keywords
- Amino Acid Sequence
- Animals
- Circular Dichroism
- Fluorescent Dyes
- Heparin
- Hydrogen-Ion Concentration
- Mice
- Micelles
- Microscopy, Atomic Force
- Oligopeptides
- Protein Multimerization
- Protein Structure, Secondary
- Spectrometry, Fluorescence
- Spectroscopy, Fourier Transform Infrared
- Surface-Active Agents
- Thiazoles