Enhanced Fibril Fragmentation of N‐Terminally Truncated and Pyroglutamyl‐Modified Aβ Peptides. Issue 16 (11th March 2016)

• Record Type: Journal Article
• Authors: Wulff, Melanie; Baumann, Monika; Thümmler, Anka; Yadav, Jay K.; Heinrich, Liesa; Knüpfer, Uwe; Schlenzig, Dagmar; Schierhorn, Angelika; Rahfeld, Jens‐Ulrich; Horn, Uwe; Balbach, Jochen; Demuth, Hans‐Ulrich; Fändrich, Marcus
• Is Part Of: Angewandte Chemie international edition. Volume 55:Issue 16(2016)
• Page Start: 5081
• Page End: 5084
• Publication Date: 2016-03-11
• Subjects: amyloids -- covalent protein modifications -- Alzheimer's disease -- peptide aggregation -- protein folding; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201511099
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: N‐terminal truncation and pyroglutamyl (pE) formation are naturally occurring chemical modifications of the Aβ peptide in Alzheimer's disease. We show herein that these two modifications significantly reduce the fibril length and the transition midpoint of thermal unfolding of the fibrils, but they do not substantially perturb the fibrillary peptide conformation. This observation implies that the N terminus of the unmodified peptide protects Aβ fibrils against mechanical stress and fragmentation and explains the high propensity of pE‐modified peptides to form small and particularly toxic aggregates. Abstract : Now we're just falling apart : A naturally occurring chemical modification (pyroglutamyl, pE) affects the aggregation properties and toxicity of the Alzheimer's disease Aβ peptide. These effects were shown not to correspond to effects on the peptide fold or secondary structure but rather to be the result of an increased fragmentation propensity of the aggregates formed by the modified peptide.