Elucidating the Amyloid formation mechanism with 2-D infrared spectroscopy

Abstract

Amyloid fiber forming proteins have been implicated as principal components of the pathogenesis of numerous human diseases. The mechanism by which these proteins disrupt cell function remains obscured, largely due to a lack of secondary structural resolution in the spectroscopies used to study fiber formation. Our capacity to take rapid, automated 2D-IR spectra affords us an ability to follow distinct secondary structure kinetics during amyloid folding and aggregation. Additionally, we have used isotope labeling to assess local structure and dynamics in the human islet amyloid polypeptide (hIAPP), an amyloid forming protein involved in type II diabetes. Our experimental findings, complimented by electronic structure calculations, provide a more complete description of the secondary structure evolution of amyloid fibers than has been made available with previously employed techniques.