TY - JOUR
T1 - Formation of dynamic soluble surfactant-induced amyloid β peptide aggregation intermediates
AU - Abelein, Axel
AU - Kaspersen, Jørn Døvling
AU - Nielsen, Søren Bang
AU - Jensen, Grethe Vestergaard
AU - Christiansen, Gunna
AU - Pedersen, Jan Skov
AU - Danielsson, Jens Albert
AU - Otzen, Daniel
AU - Gräslund, Astrid
PY - 2013/8/9
Y1 - 2013/8/9
N2 - 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.
AB - 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.
U2 - 10.1074/jbc.M113.470450
DO - 10.1074/jbc.M113.470450
M3 - Journal article
C2 - 23775077
SN - 0021-9258
VL - 288
SP - 23518
EP - 23528
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
ER -