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Tracking fiber formation in human islet amyloid polypeptide with automated 2D-IR spectroscopy.

ABSTRACT: Amyloid forming proteins have been implicated in many human diseases. The kinetics of amyloid fiber formation are of particular interest because evidence points to intermediate folding structures as potential cytotoxic species. The standard methods for monitoring the kinetics are to use fluorescence or circular dichroism spectroscopy, which do not uniquely resolve secondary structures. In this work, we use a new technology for rapidly scanning 2D-IR spectra that allows us to follow the fiber formation kinetics of the human islet amyloid polypeptide (hIAPP) that is involved in type II diabetes. Spectroscopic markers are identified that uniquely monitor random coil versus beta-sheet secondary structures as well as probe beta-sheet elongation and stacking. Our measurements provide more rigorous kinetics for the secondary structure evolution of amyloid formation than is available with other techniques.

SUBMITTER: Strasfeld DB

PROVIDER: S-EPMC3209517 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

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Tracking fiber formation in human islet amyloid polypeptide with automated 2D-IR spectroscopy.

Strasfeld David B DB Ling Yun L YL Shim Sang-Hee SH Zanni Martin T MT

Journal of the American Chemical Society 20080507 21

Amyloid forming proteins have been implicated in many human diseases. The kinetics of amyloid fiber formation are of particular interest because evidence points to intermediate folding structures as potential cytotoxic species. The standard methods for monitoring the kinetics are to use fluorescence or circular dichroism spectroscopy, which do not uniquely resolve secondary structures. In this work, we use a new technology for rapidly scanning 2D-IR spectra that allows us to follow the fiber for ...[more]

PMID: 18459774

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