Abstract

2D IR spectroscopy holds tremendous promise for elucidating the
structural kinetics of proteins, including membrane and aggregating
proteins that are difficult to study with NMR or other techniques.  In
this talk, I will report new advances in the technology of 2D IR
spectroscopy as well as its application to amyloid aggregation
kinetics.  Recently, my research group learned to collect 2D IR spectra
using a mid-infrared pulse shaper that we developed.  This novel pulse
shaper allows us to computer generate 2D IR pulse sequences with
controlled shapes, phases and, most recently, polarizations.  Computer
generation also tremendously speeds up data collection, since there are
no longer moving parts in our spectrometer.  Using this new technology,
we monitored the kinetics of fiber formation of amylin, the peptide
involved in type 2 diabetes.  By using isotope labeling, we observed
secondary structure formation with residue-specific structural
resolution.  Thus, our new technology, combined with isotope labeling,
has allowed us to map the aggregation pathway of this peptide as it
associates into fibers with unprecedented structural resolution.