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

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  • Axel Abelein, Department of Biochemistry and Biophysics, Stockholm University, Sverige
  • Jørn Døvling Kaspersen, Danmark
  • Søren Bang Nielsen
  • ,
  • Grethe Vestergaard Jensen, Danmark
  • Gunna Christiansen
  • Jan Skov Pedersen
  • Jens Albert Danielsson, MBI 2, Danmark
  • Daniel Otzen
  • Astrid Gräslund, Department of Biochemistry and Biophysics, Stockholm University, Sverige
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 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 (min to h time scale) fibrillation process, much faster dynamic exchange (kex ~ 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 towards an aggregation prone state.
OriginalsprogEngelsk
TidsskriftJournal of Biological Chemistry
Vol/bind288
Sider (fra-til)23518-23528
Antal sider11
ISSN0021-9258
DOI
StatusUdgivet - 9 aug. 2013

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