Format

Send to

Choose Destination
J Biol Chem. 2013 Aug 9;288(32):23518-28. doi: 10.1074/jbc.M113.470450. Epub 2013 Jun 17.

Formation of dynamic soluble surfactant-induced amyloid β peptide aggregation intermediates.

Author information

1
Department of Biochemistry and Biophysics, Stockholm University, Svante Arrhenius Väg 16, SE-106 91 Stockholm, Sweden.

Abstract

Intermediate amyloidogenic states along the amyloid β peptide (Aβ) aggregation pathway have been shown to be linked to neurotoxicity. To shed more light on the different structures that may arise during Aβ aggregation, we here investigate surfactant-induced Aβ aggregation. This process leads to co-aggregates featuring a β-structure motif that is characteristic for mature amyloid-like structures. Surfactants induce secondary structure in Aβ in a concentration-dependent manner, from predominantly random coil at low surfactant concentration, via β-structure to the fully formed α-helical state at high surfactant concentration. The β-rich state is the most aggregation-prone as monitored by thioflavin T fluorescence. Small angle x-ray scattering reveals initial globular structures of surfactant-Aβ co-aggregated oligomers and formation of elongated fibrils during a slow aggregation process. Alongside this slow (minutes to hours time scale) fibrillation process, much faster dynamic exchange (k(ex) ∼1100 s(-1)) takes place between free and co-aggregate-bound peptide. The two hydrophobic segments of the peptide are directly involved in the chemical exchange and interact with the hydrophobic part of the co-aggregates. Our findings suggest a model for surfactant-induced aggregation where free peptide and surfactant initially co-aggregate to dynamic globular oligomers and eventually form elongated fibrils. When interacting with β-structure promoting substances, such as surfactants, Aβ is kinetically driven toward an aggregation-prone state.

KEYWORDS:

Aggregation; Alzheimer Disease; Amyloid; Amyloid β Peptide; Circular Dichroism (CD); NMR; NMR Relaxation Dispersion; Small Angle X-ray Scattering; Surfactant

PMID:
23775077
PMCID:
PMC5395029
DOI:
10.1074/jbc.M113.470450
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center