Time-resolved infrared spectroscopy of pH-induced aggregation of the Alzheimer Abeta(1-28) peptide.
Aggregation of the Alzheimer's disease-related Abeta(1-28) peptide was induced by a rapid, sub-millisecond pH jump and monitored by time-resolved infrared spectroscopy on the millisecond to second time-scale. The release of protons was induced by the photolysis of a caged compound, 1-(2-nitrophenyl)ethyl sulfate (NPE-sulfate). The pH jump generated in our experimental setup is used to model the Abeta peptide structural conversions that may occur in the acidic endosomal/lysosomal cell compartment system. The aggregation of the Abeta(1-28) peptide induced by the pH jump from 8.5 to <6 yields an antiparallel beta-sheet structure. The kinetics of the structural transition is biphasic, showing an initial rapid phase with a transition from random coil to an oligomeric beta-sheet form with a time constant of 3.6 s. This phase is followed by a second slower transition, which yields larger aggregates during 48.0 s.
Perálvarez-Marín
Alex
A
Department of Biochemistry and Biophysics, Stockholm University, Stockholm 10691, Sweden. apm@dbb.su.se
Barth
Andreas
A
Gräslund
Astrid
A
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D009578:Nitrobenzenes / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013055:Spectrophotometry, Infrared / Q000379:methods*
C473956:1-(2-nitrophenyl)ethyl sulfate; D016229:Amyloid beta-Peptides; D009578:Nitrobenzenes; D010446:Peptide Fragments; C084358:amyloid beta-protein (1-28); C075222:amyloid beta-protein (1-42)