Abstract
Characterization of oligomeric intermediate states populated at an early stage of misfolding and aggregation is essential to understanding molecular mechanism of pathogenic protein aggregation. Growing evidence also suggests that oligomeric species are more toxic than mature fibrillar counterparts. Here, we describe procedures for isolating oligomeric species of an aggregation-prone protein, transthyretin, associated with protein misfolding disorders, including cardiomyopathy and polyneuropathy. We also describe methods for structural studies of the oligomeric species using circular dichroism and solid-state NMR spectroscopy. These methods can be applied to structural characterization of oligomeric intermediates of other aggregation-prone proteins.