Solid-state NMR reveals a close structural relationship between amyloid-ß protofibrils and oligomers.

ABSTRACT

We have studied tertiary contacts in protofibrils and mature fibrils of amyloid-ß (Aß) peptides using solid-state NMR spectroscopy. Although intraresidue contacts between Glu-22 and Ile-31 were found in Aß protofibrils, these contacts were completely absent in mature Aß fibrils. This is consistent with the current models of mature Aß fibrils. As these intramolecular contacts have also been reported in Aß oligomers, our measurements suggest that Aß protofibrils are structurally more closely related to oligomers than to mature fibrils. This suggests that some structural alterations have to take place on the pathway from Aß oligomers/protofibrils to mature fibrils, in agreement with a model that suggests a conversion of intramolecular hydrogen-bonded structures of Aß oligomers to the intermolecular stabilized mature fibrils (Hoyer, W., Grönwall, C., Jonsson, A., Ståhl, S., and Härd, T. (2008) Proc. Natl. Acad. Sci. U.S.A. 105, 5099-5104).