Direct conversion of an oligopeptide from a beta-sheet to an alpha-helix: a model for amyloid formation.

Abstract

A 16-amino acid oligopeptide forms a stable beta-sheet structure in water. In physiological solutions it is able to self-assemble to form a macroscopic matrix that stains with Congo red. On raising the temperature of the aqueous solution above 70 degrees C, an abrupt structural transition occurs in the CD spectra from a beta-sheet to a stable alpha-helix without a detectable random-coil intermediate. With cooling, it retained the alpha-helical form and took several weeks at room temperature to partially return to the beta-sheet form. Slow formation of the stable beta-sheet structure thus shows kinetic irreversibility. Such a formation of very stable beta-sheet structures is found in the amyloid of a number of neurological diseases. This oligopeptide could be a model system for studying the protein conformational changes that occurs in scrapie or Alzheimer disease. The abrupt and direct conversion from a beta-sheet to an alpha-helix may also be found in other processes, such as protein folding and protein-protein interaction. Furthermore, such drastic structure changes may also be exploited in biomaterials designed as sensors to detect environmental changes.