Abstract
We have investigated the site-specific backbone dynamics of mature amyloid β (Aβ) fibrils using solid-state NMR spectroscopy. Overall, the known β-sheet segments and the turn linking these two β-strands exhibit high order parameters between 0.8 and 0.95, suggesting low conformational flexibility. The first approximately eight N-terminal and the last C-terminal residues exhibit lower order parameters between ∼0.4 and 0.8. Interestingly, the order parameters increase again for the first two residues, Asp(1) and Ala(2), suggesting that the N terminus could carry some structural importance.
Highlights
Alzheimer disease is the most important neurodegenerative disorder; treatment approaches require atomistic knowledge of fibrillar structure and dynamics
We compared the NMR spectra of A(1– 40) fibrils grown in sodium borate buffer at pH 9 with fibrils grown in sodium phosphate buffer at pH 7.4
The NMR spectra from both fibril preparations showed signals with identical chemical shifts; the fibrils prepared in borate buffer provided slightly narrower lines in the NMR spectra
Summary
Alzheimer disease is the most important neurodegenerative disorder; treatment approaches require atomistic knowledge of fibrillar structure and dynamics. Results: We have site- studied the molecular dynamics of amyloid  (A) fibrils by solid-state NMR. Significance: Dynamics studies of A fibrils suggest a structural role of the N terminus of the peptide. We have investigated the site-specific backbone dynamics of mature amyloid  (A) fibrils using solid-state NMR spectroscopy. Only a very few reports on fibrillar dynamics in general exist so far [15, 19, 20] These studies showed that the investigation of the fibril dynamics can significantly support the structural analysis and further characterize the respective structural elements. We have studied the molecular dynamics of mature A(1– 40) fibrils in a site-specific manner using solid-state NMR spectroscopy
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