Absolute correlation between lag time and growth rate in the spontaneous formation of several amyloid-like aggregates and fibrils.
The formation of polypeptide aggregates, including amyloid fibrils and prions, is a biochemical process of considerable interest in the context of its association with ageing and neurodegeneration. Aggregation occurs typically with a lag phase and a growth phase that reflect an underlying nucleation-polymerisation mechanism. While the propensity of nucleation can be estimated from the lag time t(l), the efficiency of growth is represented by the growth rate k(g). Here, I have analysed the absolute k(g) and t(l) values from a total of 298 samples prepared from insulin, glucagon and different sequence variants of the Alzheimer's Abeta(1-40) peptide. Although these samples differ in the conditions of aggregation, systematic comparison reveals an overall similarity in the plot of k(g)versus t(l). The plot fits readily with the simple equation k(g)=alpha/t(l) and by using a proportionality factor alpha of 4.5. In contrast to the individual values of k(g) and t(l) that depend substantially on sequential and environmental parameters, alpha seems much less affected by such factors. These data suggest mechanistic similarities in the nucleation behaviour of different amyloid-like fibrils and aggregates.
Fändrich
Marcus
M
Leibniz-Institut für Altersforschung, Fritz-Lipmann Institut, Beutenbergstrasse 11, D-07745 Jena, Germany. fandrich@fli-leibniz.de
D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002417:Cattle; D005934:Glucagon / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D020836:Protein Structure, Quaternary
D000682:Amyloid; D016229:Amyloid beta-Peptides; D007328:Insulin; D050505:Mutant Proteins; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D005934:Glucagon