A long-lived A? oligomer resistant to fibrillization.

ABSTRACT: The hydrophobic A? peptide is highly aggregation prone; it first forms soluble oligomers, which then convert into the amyloid fibrils found in the cerebral plaques of Alzheimer's disease. It is generally understood that as the peptide concentration of A? increases, the fibrillization process is accelerated, but we examine the limits on this phenomenon. We found that once a threshold concentration of A? is exceeded, a stable oligomer is formed at the expense of fibril formation. The suppression of fibril formation was observed by amyloid-binding dye Thioflavin T and solution nuclear magnetic resonance (NMR). Small-angle X-ray scattering, size exclusion chromatography, and analytical ultracentrifugation demonstrated that A? peptides form a range of compact species, with a dimer being an early highly populated oligomer. Solution NMR allowed us to define the secondary structure of this A? dimer, which shows interlocking contacts between C-terminal peptide strands. Thus, we present a novel A? oligomer that resists conversion to fibrils and remains stable for more than one year.

SUBMITTER: Nick M 

PROVIDER: S-EPMC6039285 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature