The aggregation kinetics of Alzheimer's beta-amyloid peptide is controlled by stochastic nucleation.
We report here a recombinant expression system that allows production of large quantities of Alzheimer's Abeta(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.
Hortschansky
Peter
P
Institut für Molekulare Biotechnologie (IMB), Jena, Germany.
Schroeckh
Volker
V
Christopeit
Tony
T
Zandomeneghi
Giorgia
G
Fändrich
Marcus
M
D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D052160:Benzothiazoles; D002942:Circular Dichroism; D003198:Computer Simulation; D010450:Endopeptidases / Q000235:genetics; D006639:Histidine / Q000235:genetics; D006801:Humans; D007700:Kinetics; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011487:Protein Conformation; D017510:Protein Folding; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013844:Thiazoles
D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D010446:Peptide Fragments; D013844:Thiazoles; C078592:amyloid beta-protein (1-40); C009462:thioflavin T; C033223:polyhistidine; D006639:Histidine; D010450:Endopeptidases; C099488:TEV protease