Random Coils, β-Sheet Ribbons, and α-Helical Fibers:  One Peptide Adopting Three Different Secondary Structures at Will

• Published in: Journal of the American Chemical Society 2006-02, Vol.128 (7), p.2196-2197
• Main Authors: Pagel, Kevin, Wagner, Sara C, Samedov, Kerim, von Berlepsch, Hans, Böttcher, Christoph, Koksch, Beate
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Biological and medical sciences; Circular Dichroism; Conformational dynamics in molecular biology; Fundamental and applied biological sciences. Psychology; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Molecular biophysics; Molecular Sequence Data; Protein Structure, Secondary; Proteins - chemistry
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja057450h

To potentially cure neurodegenerative diseases, we need to understand on a molecular level what triggers the complex folding mechanisms and shifts the equilibrium from functional to pathological isoforms of proteins. The development of small peptide models that can serve as tools for such studies is of paramount importance. We describe the de novo design and characterization of an α-helical coiled coil based model peptide that contains structural elements of both α-helical folding and β-sheet formation. Three distinct secondary structures can be induced at will by adjustment of pH or concentration. Low concentrations at pH 4.0 yield globular particles of the unfolded peptide, while at the same pH, but at higher concentration, defined β-sheet ribbons are formed. In contrast, at high concentrations and pH 7.4, the peptide forms highly ordered α-helical fibers. Thus, this system allows one to systematically study now the consequences of the interplay between peptide and protein primary structure and environmental factors for peptide and protein folding on a molecular level.