Influence of the hydrophobic interface and transition metal ions on the conformation of amyloidogenic model peptides

The transition of α-helical or unfolded peptides and proteins to β-sheets and the subsequent amyloid formation are characteristic for neurodegenerative diseases like Alzheimer's or Parkinson's disease. The interactions of amyloidogenic peptides with surfaces such as biological membranes are considered to play an important role regarding the onset of secondary structure changes. In our project, we used a peptide designed to have specific secondary structure propensities in order to investigate the driving forces and conditions which lead to the β-sheet formation. The model peptide is able to adopt the coiled coil conformation, α-helical peptide strands that wind around each other in a superhelical structure. In addition to building principles stabilizing this α-helical conformation it also has β-sheet stabilizing features. We focused on the interactions of the peptide with the hydrophobic air-water interface. Infrared reflection absorption spectroscopy was used as a surface sensitive method and complemented with grazing incidence X-ray diffraction and reflectivity. Furthermore, the model peptide provides metal binding sites. The binding of transition metal ions leads to a local preference of certain secondary structure elements, depending on the metal ion and the geometry of metal ion binding sites. The interplay and competition of the two trigger mechanisms (1) interaction with surfaces and (2) metal ion complexation were investigated. We found that the secondary structure of the peptide strongly depends on the interactions with the hydrophobic air-water interface and the orientation imposed by it. The metal ions Zn2+ and Cu2+ were used for complexation. The structure of the peptide surface layer differs according to the bound metal ion.