Towards Determining Amyloid Fibril Structures Using Experimental Constraints from Raman Spectroscopy

This is the authors' abstract. We don't add key points for this paper.

We present structural models for three different amyloid fibril polymorphs prepared from amylin20−29 (sequence SNNFGAILSS) and amyloid-β25−35 (Aβ25−35) (sequence GSNKGAIIGLM) peptides. These models are based on amide C=O bond and Ramachandran ψ-dihedral angle data from Raman spectroscopy, which were used structural constraintsto guide molecular dynamics (MD) simulations. The resulting structural models indicate that the basic structural motif of amylin20−29 and Aβ25−35 fibrils are extended β-strands. Our data indicates that amylin20−29 forms both antiparallel and parallel β-sheet fibril polymorphs, while Aβ25−35 forms a parallel β-sheet fibril structure. Overall, our work lays the foundation for using Raman spectroscopy in conjunction with MD simulations to determine detailed molecular-level structural models of amyloid fibrils in a manner that complements gold-standard techniques such as solid-state NMR and cryogenic electron microscopy.