Figure 8.

Solid-state ¹³C NMR of Aβ42. A. 2D ¹³C DARR NMR spectrum of Aβ42 fibrils. The spectrum was obtained using fibrils formed from an equimolar mixture of two ¹³C-labeled Aβ42 peptides having the same labeling scheme as in (A–C). A crosspeak (boxed) is observed only between 2-¹³C-Gly37 and 5-¹³C-Met35, and not between 1-¹³C-Gly33 and 5-¹³C-Met35. B. 2D ¹³C DARR NMR spectrum of Aβ42 fibrils formed using only 5-¹³C-Met35 Aβ42. The samples in (A) and (B) were prepared in parallel. The absence of a crosspeak in (B) demonstrates that the crosspeak observed in (A) is not due to natural abundance ¹³C. C. Structural model of the Aβ42 fibril. The model was based on the protofilament subunit structure of Aβ42 proposed by Riek and co-workers (56) (PDB accession code 2BEG), and the solid-state NMR contacts between Met35 and Gly37. The protofilament subunits were docked with opposite orientations to satisfy the solid-state NMR constraint that only a contact between Met35 and Gly37 was observed. The docked structure was energy minimized using standard methods. The difference in the Met- Gly contacts between Aβ40 and Aβ42 results in a shift of the two protofilament subunits relative to one another in the two structures.