Laurie Buchanan, Department of Chemistry, Vanderbilt University
"Investigating peptide structure and polymorphism with 2D IR spectroscopy"
Abstract:
Over 80% of soluble human proteins undergo acetylation as a post- or co-translational modification adding an acetyl group to reactive amino acid positions or the free N-terminus. While this represents a seemingly minor change in chemical composition, these modifications can result in vastly different protein structures and function. We use two-dimensional infrared spectroscopy (2D IR) to determine the actual transition dipole strength of protein secondary structures, allowing us to detect structural changes arising from acetylation in a label-free manner. Subsequent incorporation of site-specific isotope labels enables residue-level resolution of the structural ensemble. This approach is non-perturbing to the peptide system and allows for elucidation of distinct secondary structure variations within a single peptide aggregate which otherwise appear homogenous. This insight aids our understanding of the aggregation of amyloid proteins associated with human disease and the effects of acetylation on their self-assembly.