Time-resolved infrared spectroscopy of pH-induced aggregation of the Alzheimer Abeta(1-28) peptide |
| |
Authors: | Perálvarez-Marín Alex Barth Andreas Gräslund Astrid |
| |
Affiliation: | Department of Biochemistry and Biophysics, Stockholm University, Stockholm 10691, Sweden |
| |
Abstract: | Aggregation of the Alzheimer's disease-related Aβ1-28 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 Aβ peptide structural conversions that may occur in the acidic endosomal/lysosomal cell compartment system. The aggregation of the Aβ1-28 peptide induced by the pH jump from 8.5 to < 6 yields an antiparallel β-sheet structure. The kinetics of the structural transition is biphasic, showing an initial rapid phase with a transition from random coil to an oligomeric β-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. |
| |
Keywords: | Alzheimer's disease amyloid FTIR spectroscopy endosomal/lysosomal acidification caged compounds |
本文献已被 ScienceDirect PubMed 等数据库收录! |