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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*
PLOS ONE (Internet), 11(4), p.e0151447_1 - e0151447_17, 2016/04
被引用回数:24 パーセンタイル:64.29(Multidisciplinary Sciences)Filamentous aggregates (amyloid fibrils) of the protein -synuclein (-Syn) are related to the pathogenesis of Parkinson's disease. To understand the pathogenesis mechanism of this disease, the mechanism of the amyloid fibril formation of -Syn must be elucidated. As a first step toward this ultimate goal, dynamical behavior of -Syn in the monomeric and the fibril states was investigated using quasielastic neutron scattering (QENS). Analysis of the QENS spectra of solution samples of -Syn shows that diffusive global motions are observed in the monomeric state but largely suppressed in the fibril state. However, the amplitude of the side chain motion is shown to be larger in the fibril state than in the monomeric state. This implies that significant solvent space exists within the fibrils, which is attributed to the -Syn molecules within the fibrils having a distribution of conformations. The larger amplitude of the side chain motion in the fibril state than in the monomeric state implies that the fibril state is entropically favorable.
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*
no journal, ,
A protein -synuclein (-Syn) forms amyloid fibrils. This abnormal protein aggregation is related to pathogenesis of a neuro-degenerative disorder, Parkinson's disease. Propensity for amyloid fibril formation depends on environmental conditions such as pH. We carried out quasielastic neutron scattering experiments to investigate the "dynamic" behavior of -Syn to investigate the relationship between the dynamics and propensity for amyloid fibril formation. The measurements on the solution samples of -Syn in different pH were carried out using a high energy resolution near-backscattering spectrometer, BL02 (DNA), at MLF/J-PARC, Japan. Differences in flexibility of the protein were detected between the different conditions. Since the difference in flexibility is likely to arise from different distributions of conformational substates of -Syn, the results obtained suggest an entropy-driven mechanism of the amyloid fibril formation.
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*
no journal, ,
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.
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*
no journal, ,
The protein, -synuclein (-Syn) forms amyloid fibrils. Formation of amyloid fibrils is associated with the pathogenesis of a neuro-degenerative disorder, Parkinson's disease. In order to obtain insights into the role of the protein dynamics in the mechanism of amyloid fibril formation, we carried out quasielastic neutron scattering experiments and characterized the "dynamic" behavior of -Syn. The measurements on the solution samples of -Syn in the monomeric and fibril states were carried out using a high energy resolution near-backscattering spectrometer, BL02 (DNA), at MLF/J-PARC, Japan. Differences in the dynamical behavior of the protein were detected between the monomeric and fibril states. Analysis of the spectra obtained suggested an entropy-driven mechanism of amyloid fibril formation.