Alpha-sheet: The toxic conformer in amyloid diseases?

A novel secondary structure, the alpha-sheet, was identified through molecular dynamics (MD) simulations of various proteins associated with amyloid diseases under amyloidogenic conditions. The structure was first predicted by Pauling and Corey, and it has been directly observed in crystal structures of "nonnatural peptides". There are occurrences of alpha-strands and alpha-sheets in the Protein Data Bank, but they are rare. We propose that alpha-sheet is formed during the conformational changes associated with amyloidosis and that it may represent the toxic conformer. Here, structural properties of the alpha-sheet, background information, and experimental support for this novel structure are presented. Finally we speculate about the possible role of this conformation in disease.