Dynamical behavior of human -synuclein studied by quasielastic neutron scattering

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

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.