Experimental Evidence for the Reorganization of β-Strands within Aggregates of the Aβ(16−22) Peptide

Amyloidogenic deposits that accumulate in brain tissue with the progression of Alzheimer's disease contain large amounts of the amyloid β-peptide. A small fragment of this peptide, comprising residues 16−22 (Aβ(16−22)), forms β-sheets in isolation, which then aggregate into amyloid fibrils. Her...

Full description

Saved in:
Bibliographic Details
Published in:Journal of the American Chemical Society 2005-10, Vol.127 (39), p.13488-13489
Main Authors: Petty, Sarah A, Decatur, Sean M
Format: Article
Language:English
Subjects:
Biological and medical sciences
Fundamental and applied biological sciences. Psychology
Interactions. Associations
Intermolecular phenomena
Molecular biophysics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Amyloidogenic deposits that accumulate in brain tissue with the progression of Alzheimer's disease contain large amounts of the amyloid β-peptide. A small fragment of this peptide, comprising residues 16−22 (Aβ(16−22)), forms β-sheets in isolation, which then aggregate into amyloid fibrils. Here, using isotope edited infrared spectroscopy to probe the secondary structure of the peptide with residue level specificity, we are able to show conclusively that the β-sheets formed are antiparallel and, following an anneal cycle or prolonged incubation, are in register with the central residue (Phe19) in alignment across all strands. The alignment of strands proceeds via a rapid interchange from one sheet to another. This realignment of the peptide strands into a more favorable registry may have important implications for therapeutics since previous work has shown that well aligned β-sheets form more stable amyloid fibrils.
ISSN:0002-7863
1520-5126
DOI:10.1021/ja054663y