α-Sheet: The Toxic Conformer in Amyloid Diseases?
- 22 July 2006
- journal article
- review article
- Published by American Chemical Society (ACS) in Accounts of Chemical Research
- Vol. 39 (9) , 594-602
- https://doi.org/10.1021/ar0500719
Abstract
A novel secondary structure, the α-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 α-strands and α-sheets in the Protein Data Bank, but they are rare. We propose that α-sheet is formed during the conformational changes associated with amyloidosis and that it may represent the toxic conformer. Here, structural properties of the α-sheet, background information, and experimental support for this novel structure are presented. Finally we speculate about the possible role of this conformation in disease.Keywords
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