Cross-⍺/β Polymorphism of PSMα3 Fibrils

Abstract

The formation of ordered cross-β amyloid protein aggregates is associated with a variety of human disorders. While conventional infrared methods serve as sensitive reporters of the presence of these amyloids, the recently discovered amyloid secondary structure of cross- fibrils presents new questions and challenges. Herein, we report results using Fourier Transform infrared (FTIR) spectroscopy and two-dimensional infrared (2DIR) spectroscopy, to monitor the aggregation of one such cross-alpha forming peptide, phenol soluble modulin alpha 3 (PSM⍺3). Phenol soluble modulins (PSMs) are involved in the formation and stabilization of Staphylococcus aureus biofilms, making sensitive methods of detecting and characterizing these fibrils a pressing need. Our experimental data, coupled with spectroscopic simulations, reveals the simultaneous presence of cross-⍺ and cross-β polymorphs within samples of PSM⍺3 fibrils. We also report a new spectroscopic feature indicative of cross-alpha fibrils.

The application of the hierarchical approach for the construction of foldameric peptide self-assembled nanostructures

“…27 The presence of a b-sheet component was also observed in the case of cross-a peptides such as PSMa3. 36 The percentage area of this subband clearly distinguishes coiled-coil oligomers from fibrils. The presence of both amide features arising from helical and intermolecular aggregates confirmed that a,b-peptide structures can form fibrils.…”

“…Interestingly, not all stained structures exhibit birefringence under polarized light, which is characteristic of amyloids in tissues. 36,44 For peptides 1_b and 2_b, it was difficult to observe formed structures, presumably because shorter fibrils (a few mm long) may not be visible at the 200Â magnification during imaging. 45 All the bright structures seen in the background of the samples that do not resemble fibrils are likely to be smaller structures that bind to CR dye.…”