Speaker
Description
The combination of incoherent neutron scattering (INS) and selective deuterium labelling is a powerful tool that puts the focus either on protein or on water motions on the ns-ps time scale and allows their dynamic coupling to be studied (Schiro et al. (2015) Nat Com 6, 6490). We have started focusing on the hydration-water dynamics of those proteins that can form the pathological fibers involved in so-called protein aggregation diseases, such as the intrinsically disordered proteins tau (Alzheimer’s) and α-synuclein (Parkinson’s). So far, evidence has been found that hydration water mobility is enhanced around tau amyloid fibers, a finding that identifies hydration water entropy as a potentially universal driving force behind fiber formation (Fichou et al. (2015) PNAS 112, 6365). Recently, we extended our study to α-synuclein and combined INS on SPHERES (MLZ) with molecular dynamics simulations on full-length monomers and fibers (Pounot, Forsyth, Härtlein, Langkilde, Marasini, Moulin, Schiro, Seydel, Tobias, Vestergaard, Weik, Zamponi, unpublished). Ongoing efforts aim at following changes in protein dynamics during fiber formation in situ by time-resolved neutron backscattering. A proof-of-principle study on lysozyme was successfully carried out on IN16B (ILL) and shows that the apparent diffusion coefficient decreases monotonically during fiber formation, whereas internal protein dynamics remain unchanged (Pounot, Chaaban, Fodera, Schiro, Seydel, Weik, unpublished).
