Changes in the dynamics of human -synuclein and its relation to propensity for amyloid fibril formation

Fujiwara, Satoru; Araki, Katsuya*; Matsuo, Tatsuhito; Yagi, Hisashi*; Yamada, Takeshi*; Shibata, Kaoru  ; Mochizuki, Hideki*

A protein -synuclein (-Syn), which is involved with pathogenesis of a neuro-degenerative disorder, Parkinson's disease, forms amyloid fibrils. Propensity for amyloid fibril formation depends on environmental conditions such as pH. We employed neutron scattering to investigate the "dynamic" behavior of -Syn at low and neutral pH, to investigate the relationship between the dynamics and propensity for amyloid fibril formation. We carried out the quasielastic neutron scattering experiments using a high energy resolution near-backscattering spectrometer, BL02 (DNA), at MLF/J-PARC, Japan. Analysis of the quasielasitc scattering spectra showed the increased flexibility of -Syn at low pH. Since the increased flexibility is likely to arise from a wider distribution of conformational substates of -Syn, the results obtained suggest an entropy-driven mechanism of the amyloid fibril formation.