Secondary structure conversions of Alzheimer's Abeta(1-40) peptide induced by membrane-mimicking detergents.
The amyloid beta peptide (Abeta) with 39-42 residues is the major component of amyloid plaques found in brains of Alzheimer's disease patients, and soluble oligomeric peptide aggregates mediate toxic effects on neurons. The Abeta aggregation involves a conformational change of the peptide structure to beta-sheet. In the present study, we report on the effect of detergents on the structure transitions of Abeta, to mimic the effects that biomembranes may have. In vitro, monomeric Abeta(1-40) in a dilute aqueous solution is weakly structured. By gradually adding small amounts of sodium dodecyl sulfate (SDS) or lithium dodecyl sulfate to a dilute aqueous solution, Abeta(1-40) is converted to beta-sheet, as observed by CD at 3 degrees C and 20 degrees C. The transition is mainly a two-state process, as revealed by approximately isodichroic points in the titrations. Abeta(1-40) loses almost all NMR signals at dodecyl sulfate concentrations giving rise to the optimal beta-sheet content (approximate detergent/peptide ratio = 20). Under these conditions, thioflavin T fluorescence measurements indicate a maximum of aggregated amyloid-like structures. The loss of NMR signals suggests that these are also involved in intermediate chemical exchange. Transverse relaxation optimized spectroscopy NMR spectra indicate that the C-terminal residues are more dynamic than the others. By further addition of SDS or lithium dodecyl sulfate reaching concentrations close to the critical micellar concentration, CD, NMR and FTIR spectra show that the peptide rearranges to form a micelle-bound structure with alpha-helical segments, similar to the secondary structures formed when a high concentration of detergent is added directly to the peptide solution.
Wahlström
Anna
A
Department of Biochemistry and Biophysics, The Arrhenius Laboratories for Natural Sciences, Stockholm University, Sweden.
Hugonin
Loïc
L
Perálvarez-Marín
Alex
A
Jarvet
Jüri
J
Gräslund
Astrid
A
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D003902:Detergents / Q000494:pharmacology*; D008567:Membranes, Artificial; D008823:Micelles; D017433:Protein Structure, Secondary / Q000187:drug effects; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013057:Spectrum Analysis; D013696:Temperature
D016229:Amyloid beta-Peptides; D003902:Detergents; D008567:Membranes, Artificial; D008823:Micelles; D012967:Sodium Dodecyl Sulfate; C028913:dodecyl sulfate