Umbrella-like helical structure of alpha-synuclein at the air-water interface observed with experimental and theoretical sum frequency generation spectroscopy (original) (raw)

The misfolding of ⍺-synuclein (aS) into amyloid aggregates is associated with severe brain disorders. Aggregat-ed copies of aS are found in the amyloid aggregates observed in brain tissues from Parkinson’s patients. Surfaces are known to catalyze the formation of amyloid aS aggregates. Despite the importance of the role of inter-faces and several decades of structural studies, the 3D structure of aS when bound to interfaces is still not completely clear. Hydrophobic interfaces are particularly important here. We report interface-specific sum-frequency generation (SFG) experiments to determine how monomeric aS binds to the air-water interface, a model system for hydrophobic surfaces in general. We model the SFG data by combining the experimental data directly to theoretical spectra calculations from molecular dynamics simulations. We find that aS, which is an intrinsically disordered protein in solution, folds into a defined, mostly helical, secondary structure at the air-water inter...