α-Sheet: The Toxic Conformer in Amyloid Diseases?

2006/07/22 by Valerie Daggett · 5 citations
Biochemistry, Genetics and Molecular Biology · Materials Science · Medicine · #Alzheimer's disease research and treatments #Enzyme Structure and Function #Protein Structure and Dynamics

paper · doi:10.1021/ar0500719

openalex publication_date 2006/07/22 · openalex created_date 2016/06/24 · openalex updated_date 2026/07/15

Abstract

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.

Citations

• PROCHECK: a program to check the stereochemical quality of protein structures
• Pauling and Corey's α-pleated sheet structure may define the prefibrillar amyloidogenic intermediate in amyloid disease
• The Structure of the Potassium Channel: Molecular Basis of K + Conduction and Selectivity
• The Structure of Feather Rachis Keratin

Cited by

• Possible Existence of α-Sheets in the Amyloid Fibrils Formed by a TTR105–115 Mutant
• The α‐sheet: A missing‐in‐action secondary structure?
• α-Sheet secondary structure in amyloid β-peptide drives aggregation and toxicity in Alzheimer’s disease
• Chemical and Physical Variability in Structural Isomers of an l/d α-Sheet Peptide Designed To Inhibit Amyloidogenesis
• Alpha sheet [wikipedia]