2DIR spectroscopy of human amylin fibrils reflects stable β-sheet structure

Lu Wang, Chris T. Middleton, Sadanand Singh, Allam S. Reddy, Ann M. Woys, David B. Strasfeld, Peter Marek, Daniel P. Raleigh, Juan J. De Pablo, Martin T. Zanni, James L. Skinner

Research output: Contribution to journalArticlepeer-review

91 Scopus citations


The aggregation of human amylin to form amyloid contributes to islet β-cell dysfunction in type 2 diabetes. Studies of amyloid formation have been hindered by the low structural resolution or relatively modest time resolution of standard methods. Two-dimensional infrared (2DIR) spectroscopy, with its sensitivity to protein secondary structures and its intrinsic fast time resolution, is capable of capturing structural changes during the aggregation process. Moreover, isotope labeling enables the measurement of residue-specific information. The diagonal line widths of 2DIR spectra contain information about dynamics and structural heterogeneity of the system. We illustrate the power of a combined atomistic molecular dynamics simulation and theoretical and experimental 2DIR approach by analyzing the variation in diagonal line widths of individual amide I modes in a series of labeled samples of amylin amyloid fibrils. The theoretical and experimental 2DIR line widths suggest a "W" pattern, as a function of residue number. We show that large line widths result from substantial structural disorder and that this pattern is indicative of the stable secondary structure of the two β-sheet regions. This work provides a protocol for bridging MD simulation and 2DIR experiments for future aggregation studies.

Original languageEnglish (US)
Pages (from-to)16062-16071
Number of pages10
JournalJournal of the American Chemical Society
Issue number40
StatePublished - Oct 12 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Fingerprint Dive into the research topics of '2DIR spectroscopy of human amylin fibrils reflects stable β-sheet structure'. Together they form a unique fingerprint.

Cite this