The aggregation kinetics of Alzheimer's β-amyloid peptide is controlled by stochastic nucleation

被引:217
作者
Hortschansky, P
Schroeckh, V
Christopeit, T
Zandomeneghi, G
Fändrich, M
机构
[1] IMB, D-07745 Jena, Germany
[2] Leibniz Inst Nat Forschung & Infekt Biol, Hans Knoll Inst, D-07745 Jena, Germany
关键词
amyloid; conformational disease; kinetics; protein folding; prion;
D O I
10.1110/ps.041266605
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We report here a recombinant expression system that allows production of large quantities of Alzheimer's A beta(1-40) peptide. The material is competent to dissolve in water solutions with "random-coil properties," although its conformation and factual oligomerization state are determined by the physico-chemical solution conditions. When dissolved in 50 mM sodium phosphate buffer (pH 7.4) at 37 degrees C, the peptide is able to undergo a nucleated polymerization reaction. The aggregation profile is characteristically bipartite, consisting of lag and growth phase. From these curves we determined the lag time as well as the rate of aggregation. Both values were found to depend on peptide concentration and addition or formation of seeds. Moreover, they can vary considerably between apparently identical samples. These data imply that the nucleation event is under influence of a stochastic factor that can manifest itself in profound macroscopic differences in the aggregation kinetics of otherwise indistinguishable samples.
引用
收藏
页码:1753 / 1759
页数:7
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