A long-lived Aß oligomer resistant to fibrillization.
Biopolymers
; 109(8): e23096, 2018 Aug.
Article
en En
| MEDLINE
| ID: mdl-29319162
ABSTRACT
The hydrophobic Aß 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 Aß increases, the fibrillization process is accelerated, but we examine the limits on this phenomenon. We found that once a threshold concentration of Aß 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 Aß 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 Aß dimer, which shows interlocking contacts between C-terminal peptide strands. Thus, we present a novel Aß oligomer that resists conversion to fibrils and remains stable for more than one year.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
/
Péptidos beta-Amiloides
/
Resonancia Magnética Nuclear Biomolecular
/
Benzotiazoles
/
Agregado de Proteínas
Límite:
Humans
Idioma:
En
Revista:
Biopolymers
Año:
2018
Tipo del documento:
Article