Dynamics of Serine-8 Side-Chain in Amyloid-β Fibrils and Fluorenylmethyloxycarbonyl Serine Amino Acid, Investigated by Solid-State Deuteron NMR.

Serine side-chains are strategic sites of post-translational modifications, and it is important to establish benchmarks of their internal dynamics. In this work, we compare the dynamics of serine side-chains in several biologically important systems: serine-8 in the disordered domain of Aβ1-40 fibrils in the hydrated and dry states and fluorenylmethyloxycarbonyl (Fmoc) serine with the bulky group that mimics the hydrophobicity of the fibril contacts yet lacks the complexity of the protein system. Using deuterium solid-state NMR static line shape and longitudinal relaxation techniques in the 310 to 180 K temperature range, we compare the main features of the dynamics in these systems. The main motional modes in the fibrils are large-scale fluctuations in the hydrated state of the fibrils as well as local motions such as 3-site jumps of the Cβ deuterons at high temperatures and small-angle fluctuations of the Cα-Cβ axis at low temperatures. In the hydrated fibrils, two distinct states are present with vastly different extents of large-scale diffusive motions and 3-site-jump rate constants. The hydrated state at the physiological conditions is dominated by the "free" state undergoing large-scale diffusive motions and very fast local 3-site jumps, while in the "bound" state, these large-scale motions are quenched due to transient inter- and intramolecular interactions. Additionally, in the bound state, the 3-site-jump motions are orders of magnitude slower. Details of the dynamics in the serine side-chain are dependent on fine structural features and hydration levels of the systems.