Experimental analysis of conformational evolution process of a prion by developing the kinetic NMR

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In order to elucidate the conformational conversion process of a prion protein from its cellular form to the pathogenic one and the prion's evolution mechanism, we created a series of novel apparatuses, i.e. kinetic fluorescence, kinetic CD, kinetic DLS, and kinetic NMR (800 MHz). Using these novel analytical systems, we could detect the early conformational changes in a prion protein prior to the aggregation formation. Using the kinetic DLS, we detected the transient formation of disordered assembly before the stable amyloid-like aggregate formation. Using the kinetic NMR, we could detect the region specific degradation of the peptide bonds by imposing the ultrasonication. Those phenomena would give us important clues for understanding the mechanism of conformational conversion as well as that of evolution.