The Arctic mutation alters helix length and type in the 11–28 β-amyloid peptide monomer—CD, NMR and MD studies in an SDS micelle

β-Amyloid Monomers Are Neuroprotective

“…In contrast, the substitution of a charged with a neutral amino acid (E22G) in the central portion of the Arctic peptides might have caused a substantial change in polypeptide conformational features [i.e., a more bent structure as suggested by AFM imaging (see supplemental Fig. 2, available at www.jneurosci.org as supplemental material) (see also Rodziewicz-Motowidło et al, 2008)] associated with a complete loss of neuroprotective activity. This, combined with the rapid aggregation kinetics of the Arctic peptide (Nilsberth et al, 2001;Rodziewicz-Motowidło et al, 2008), might explain the aggressive and early-onset AD associated with this mutation.…”

“…2, available at www.jneurosci.org as supplemental material) (see also Rodziewicz-Motowidło et al, 2008)] associated with a complete loss of neuroprotective activity. This, combined with the rapid aggregation kinetics of the Arctic peptide (Nilsberth et al, 2001;Rodziewicz-Motowidło et al, 2008), might explain the aggressive and early-onset AD associated with this mutation.…”

Impact of Mutations on the Conformational Transition from α-Helix to β-Sheet Structures in Arctic-Type Aβ40: Insights from Molecular Dynamics Simulations

“…The lower sampling of helical conformation (7%) in [G22]Aβ 40 is consistent with the results reported by Rodziewicz-Motowidło et al , which highlighted that E22G mutation lead to shortening of the α-helical fragment. 14 …”

“…Out of the above-listed single-point mutations, Arctic-type (E22G) mutation can be examined to obtain key insights into Aβ oligomerization and aggregation processes as Arctic-type Aβ easily form soluble Aβ protofibrils in vitro and has a purely cognitive phenotype typical of AD. 14,15 E22G mutation in Aβ peptide lead to enhanced Aβ aggregation with an increased amount of soluble oligomeric species of Aβ fibrillization. 16,17 A recent study demonstrated the effect of E22G substitution in Aβ 40 2.2.…”

“…41 The average values of the 3 J NH−Hα coupling constant of [G22]Aβ 40 residues were evaluated and compared with NMR data reported by Rodziewicz-Motowidło and co-workers in 2008 (Figure S2, Supporting Information). 14 The average value of computational 3 J NH−Hα was noted to be 7.50 Hz as compared to 7.41 Hz from the experimental data, which indicate the consistency of structural ensembles with the experiment.…”