Molecular Structure of a Fibrillar Alzheimer's Aβ Fragment

• Published in: Biochemistry (Easton) Vol. 39; no. 43; pp. 13269 - 13275
• Main Authors: Serpell, Louise C, Blake, Colin C. F, Fraser, Paul E
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 31.10.2000
• Subjects: Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Amino Acid Sequence; Amyloid beta-Peptides - chemical synthesis; Amyloid beta-Peptides - chemistry; Computer Simulation; Crystallization; Humans; Magnetics; Models, Molecular; Molecular Sequence Data; Neurofibrils - chemistry; Peptide Fragments - chemical synthesis; Peptide Fragments - chemistry; Protein Structure, Secondary; Protein Structure, Tertiary; Software; X-Ray Diffraction
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi000637v

Amyloid-β (Aβ) peptide deposition as fibrillar senile plaques is a key element in the pathology of Alzheimer's disease. Here we present a high-resolution structure of an Aβ amyloid fibril using magnetically aligned preparations of a central Aβ domain which forms representative amyloid fibrils. Diffraction analysis of these samples revealed Bragg reflections on layer lines consistent with a preferred orientation, as opposed to the typical symmetry associated with fibers. These crystalline properties permitted a molecular replacement approach based upon a β-hairpin motif resulting in a structure of the fibrillar Aβ peptide. This detailed molecular structure of Aβ in its fibrous state provides clues as to the mechanism of amyloid assembly and identifies potential targets for controlling the aggregation process.