Structural, Dynamic Properties of Key Residues in Aβ Amyloidogenesis: Implications of an Important Role of Nanosecond Timescale Dynamics

Solid-support Electron Paramagnetic Resonance (EPR) Studies of Aβ40 Monomers Reveal a Structured State with Three Ordered Segments

“…Methyl dynamics also showed relatively high rigidity at residues 30 and 31 (13). The region 29 -33 was found to have high potential to form a 3 10 helix in an MD study of A␤42 (49). Another MD study of A␤40 shows interactions between residues Ile-31-Ile-32 and Val-18 (50).…”

“…Zhang et al (11) used NMR to show that A␤ 10 -35 forms collapsed structures at the central hydrophobic cluster. On the other hand, other NMR studies revealed only increased structural propensities at localized short amino acid stretches (7)(8)(9)(10). Limited proteolysis studies by Lazo et al (15) show that residues 21-30 are protected in A␤40 sequence.…”

“…The findings from these studies, however, are often found to contradict one another, probably because of different experimental conditions. A␤ in aqueous solutions has been shown to adopt a mostly random extended structure with circular dichroism spectroscopy and NMR (7)(8)(9)(10)(11)(12)(13)(14). Zhang et al (11) used NMR to show that A␤ 10 -35 forms collapsed structures at the central hydrophobic cluster.…”

“…It was further proposed that the formation of a ␤-hairpin with two short strands at residues 31-34 and 38 -41 rigidified the C terminus of A␤42 (18). Recently, Vivekanandan et al (19) used NMR to show that the segment 13-23 adopts a 3 10 helix structure in A␤40.…”

Phosphorylation Interferes with Maturation of Amyloid-β Fibrillar Structure in the N Terminus

“…Of special interest in this study is the segment Ser 8 -Val 12 , which adopts a transient turnlike structure (32,33) and thereby partially brings the FIGURE 8. A smaller amount of pS8A␤ than npA␤ is incorporated into insoluble A␤ aggregates as indicated by one-dimensional proton NMR spectra of npA␤ (black) and pS8A␤ (gray).…”