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A common pathway for detergent-assisted oligomerization of Aβ42

Amyloid beta (Aβ) aggregation is a slow process without seeding or assisted nucleation. Sodium dodecyl sulfate (SDS) micelles stabilize Aβ42 small oligomers (in the dimer to tetramer range); subsequent SDS removal leads to a 150-kD Aβ42 oligomer. Dodecylphosphorylcholine (DPC) micelles also stabiliz...

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Detalles Bibliográficos
Autores principales: Muhammedkutty, Fidha Nazreen Kunnath, Prasad, Ramesh, Gao, Yuan, Sudarshan, Tarunya Rao, Robang, Alicia S., Watzlawik, Jens O., Rosenberry, Terrone L., Paravastu, Anant K., Zhou, Huan-Xiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663524/
https://www.ncbi.nlm.nih.gov/pubmed/37989804
http://dx.doi.org/10.1038/s42003-023-05556-w
Descripción
Sumario:Amyloid beta (Aβ) aggregation is a slow process without seeding or assisted nucleation. Sodium dodecyl sulfate (SDS) micelles stabilize Aβ42 small oligomers (in the dimer to tetramer range); subsequent SDS removal leads to a 150-kD Aβ42 oligomer. Dodecylphosphorylcholine (DPC) micelles also stabilize an Aβ42 tetramer. Here we investigate the detergent-assisted oligomerization pathway by solid-state NMR spectroscopy and molecular dynamics simulations. SDS- and DPC-induced oligomers have the same structure, implying a common oligomerization pathway. An antiparallel β-sheet formed by the C-terminal region, the only stable structure in SDS and DPC micelles, is directly incorporated into the 150-kD oligomer. Three Gly residues (at positions 33, 37, and 38) create holes that are filled by the SDS and DPC hydrocarbon tails, thereby turning a potentially destabilizing feature into a stabilizing factor. These observations have implications for endogenous Aβ aggregation at cellular interfaces.