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

ヒト-シヌクレインのダイナミクス変化とアミロイド線維形成しやすさとの関係

藤原 悟; 荒木 克哉*; 松尾 龍人; 八木 寿梓*; 山田 武*; 柴田 薫  ; 望月 秀樹*

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.