Effect of FAD mutations
on the structure and dynamics of Aβ40
variants. (a) Combined 15N and 1H chemical shift
deviation (CSD) of D23N-, E22G-, and ΔE22-Aβ40 peptides
with respect to the wild-type-Aβ40, showing significant chemical
shift differences around the respective mutation sites and to a lower
extent around residues H14-L17. The dashed line represents the noise
level in chemical shift values. For the sake of visibility, the CSD
value of residue 22 in the E22G-Aβ40 peptide has been scaled
down by a factor of 4. (b) The strand propensity of wild-type-, D23N-,
E22G-, and ΔE22-Aβ40, calculated on the basis of their
backbone (CO, Cα, N, HN, Hα) plus Cβ chemical shifts.
The shaded area shows how the respective mutations alter the strand
propensity around the site of mutation (see also Supplementary Figure S3). (c) Residue-specific 15N transverse relaxation (R2) rates of
Aβ40 variants measured at 278 K. Note the larger R2 of D23N-Aβ40 and smaller R2 of E22G-Aβ40 around the mutation site (shaded area),
indicating respectively their relative rigidity and flexibility when
compared with the wild-type-Aβ40. The relative rigidity of the
D23N-Aβ40 variant extends further proximally to Q15-K16.