Dynamics of amyloid β fibrils revealed by solid-state NMR - PubMed (original) (raw)

Dynamics of amyloid β fibrils revealed by solid-state NMR

Holger A Scheidt et al. J Biol Chem. 2012.

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.

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Figures

FIGURE 1.

FIGURE 1.

Transmission electron micrographs of fibrils of Aβ(1–40). Shown are four different peptide preparations, made of Aβ peptides with varying isotopic labeling patterns (see “Experimental Procedures”).

FIGURE 2.

FIGURE 2.

Plot of 13Cα-1H order parameters for mature Aβ(1–40) fibrils at hydration level of 50 weight % as determined from quantitative measurements of 13Cα-1H dipolar couplings by DIPSHIFT experiment. Regions with a known β-sheet structure are highlighted. The error bars represent the uncertainty of the fitting procedure of the MAS time domain signals.

FIGURE 3.

FIGURE 3.

Secondary 13C MAS NMR isotropic chemical shift values for Cα (□) and Cβ (●) for mature Aβ(1–40) fibrils at hydration level of 50 weight %. Data are given as the difference between a measured chemical shift for a specific amino acid and random coil chemical shifts taken from literature. Regions that are in agreement with β-sheet secondary structure are highlighted.

FIGURE 4.

FIGURE 4.

Plot of 13C MAS NMR line widths (full-widths at half-maximum) for Cα (□) and Cβ (●) for mature Aβ(1–40) fibrils at hydration level of 50 weight %. Regions that are in agreement with β-sheet secondary structure are highlighted.

FIGURE 5.

FIGURE 5.

Schematic representation of backbone 13Cα-1H order parameters along structure of mature Aβ(1–40) fibrils. The thick straight lines represent the two β-sheets that have been identified in solid-state NMR studies (1, 3, 5). The thin freehand lines represent the unstructured N terminus and the loop region connecting the two sheets.

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