Effect of lysine-28 side-chain acetylation on the nanomechanical behavior of alzheimer amyloid beta25-35 fibrils.
Amyloid fibrils are self-associating filamentous structures formed from the 39- to 42-residue-long amyloid beta peptide (Abeta peptide). The deposition of Abeta fibrils is one of the most important factors in the pathogenesis of Alzheimer's disease. Abeta25-35 is a fibril-forming peptide that is thought to represent the biologically active, toxic form of the full-length Abeta peptide. We have recently shown that beta sheets can be mechanically unzipped from the fibril surface with constant forces in a reversible transition, and the unzipping forces differ in fibrils composed of different peptides. In the present work, we explored the effect of epsilon-amino acetylation of the Lys28 residue on the magnitude of the unzipping force of Abeta25-35 fibrils. Although the gross structure of the Lys28-acetylated (Abeta25-35_K28Ac) and wild-type Abeta25-35 (Abeta25-35wt) fibrils were similar, as revealed by atomic force microscopy, the fundamental unzipping forces were significantly lower for Abeta25-35_K28Ac (20 +/- 4 pN SD) than for Abeta25-35wt (42 +/- 9 pN SD). Simulations based on a simple two-state model suggest that the decreased unzipping forces, caused most likely by steric constraints, are likely due to a destabilized zippered state of the fibril.
Karsai
A
A
Department of Biophysics, University of Pécs, Faculty of Medicine, Pécs, H-7624 Hungary.
Nagy
A
A
Kengyel
A
A
Mártonfalvi
Z
Z
Grama
L
L
Penke
B
B
Kellermayer
M S Z
MS
D000107:Acetylation; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D001696:Biomechanical Phenomena; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003198:Computer Simulation; D008239:Lysine / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D009010:Monte Carlo Method; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation; D013499:Surface Properties
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D008239:Lysine