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-amyloid peptide is controlled by stochastic nucleation
1 Institut für Molekulare Biotechnologie (IMB), D-07745 Jena, Germany
2 Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie, Hans-Knöll-Institut, D-07745 Jena, Germany
(RECEIVED December 1, 2004; FINAL REVISION March 31, 2005; ACCEPTED April 11, 2005)
We report here a recombinant expression system that allows production of large quantities of Alzheimer’s A
(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°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.
Keywords: amyloid; conformational disease; kinetics; protein folding; prion
Article published online ahead of print. Article and publication date are at http://www.proteinscience.org/cgi/doi/10.1110/ps.041266605.
Reprint requests to: Marcus Fändrich, Institut für Molekulare Biotechnologie (IMB), Beutenbergstraße 11, D-07745 Jena, Germany; e-mail: fandrich{at}imb-jena.de; fax: 49-3641-656310.
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