Speaker
Description
Protein amyloid fiber formation is the pathological hallmark in various neurodegenerative diseases such as Parkinson’s or Alzheimer’s. The physico-chemical origin of protein fibrillation, as well as the role that hydration-water might play remain elusive. We combined neutron spectroscopy and molecular dynamics simulations on hydrated powders of α-synuclein and tau to investigate both structural and dynamical properties of the protein-hydration water system. Hydration-water dynamics is enhanced in the fiber state of both α-synuclein and tau, as shown by increased water mean-square displacements and broader quasi-elastic neutron scattering spectra. Molecular dynamics simulations of hydrated α-synuclein powders evidence a compact monomeric state and a more extended fiber state, in which interaction between the NAC segment and the N-terminal and C-terminal regions is reduced. As a consequence, water around N-terminal and C-terminal is no more constrained by the hydrophobic residues in the NAC segment, resulting in increased dynamics and entropy. The increase in water dynamics upon fiber formation is larger for tau than for α-synuclein. Since the latter contains a much smaller fraction of disordered residues in the fiber state than the former, we suggest that residual fiber disorder correlates with hydration water dynamics. The entropic driving force that increased water dynamics presents for fiber formation is suggested to be maximized in amyloids with an extensive fuzzy coat such as tau.
