Site-specific kinetic studies of Amyloid fibril formation revealed with 2-D IR spectroscopy

PHYS 348

Sang-Hee Shim, shim@chem.wisc.edu, Department of Chemistry, University of Wisconsin, Madison, 1101 University Ave, Madison, WI 53706, David B Strasfeld, strasfeld@wisc.edu, Department of Chemistry, University of Wisconsin - Madison, 1101 University Ave., Madison, WI 53706, Yun Ling, yling@wisc.edu, Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706, and Martin T. Zanni, zanni@chem.wisc.edu, Department of Chemistry, University of Wisconsin, 1101 University Ave., Madison, WI 53706.
Amyloid fibril folding plays a central role in a number of degenerative diseases, yet little is known about detailed structural picture of its process or intermediates. We study human islet amyloid polypeptide (hIAPP) from type II diabetes using site-specific isotope labeling and two dimensional infrared (2D IR) spectroscopy. The amide I band interrogates the overall conformation changes of hIAPP during folding, which are revealed by the diagonal and off-diagonal peaks with rapid scanning 2D IR spectroscopy. We have begun applying isotope labeling to this problem, to uncover residue-specific secondary structural and environmental changes of hIAPP equilibrium and folding kinetics. Our method is providing unprecedented insight into hIAPP folding kinetics.
 

PHYS Poster Session - Optical Probes of Dynamics in Complex Environments
7:30 PM-10:00 PM, Wednesday, April 9, 2008 Morial Convention Center -- Hall A, Poster

Division of Physical Chemistry

The 235th ACS National Meeting, New Orleans, LA, April 6-10, 2008