Structural motif of polyglutamine amyloid fibrils discerned with mixed-isotope infrared spectroscopy

Expanded polyglutamine (polyQ) tracts in proteins are associated with many neurodegenerative diseases, including Huntington disease. The structure and dynamics of polyQ peptides are difficult to study due to the homogenous nature of the sequence and their high propensity to aggregate into amyloid fibrils. In this manuscript, we study mixtures of isotope-labeled peptides with 2D IR spectroscopy to resolve the structure of individual monomers within the polyQ. These results, in combination with spectra calculated from molecular-dynamics simulations, determine the dominant structure of polyQ fibrils consists of stacked β-hairpins.