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Characterization of amyloidogenic intermediate states through a combined use of CD and NMR spectroscopy

Authors
Journal
Biophysical Chemistry
0301-4622
Publisher
Elsevier
Volume
151
Issue
3
Identifiers
DOI: 10.1016/j.bpc.2010.06.007
Keywords
  • Sh3 Domain
  • Amyloidogenic Intermediate
  • Protein Misfolding
  • Nmr Spectroscopy
  • Cd Spectroscopy
  • Amyloid
Disciplines
  • Physics

Abstract

Abstract Characterization of amyloidogenic intermediate states is of central importance in understanding the molecular mechanism of amyloid formation. In this study, we utilized CD and NMR spectroscopy to investigate secondary structure of the monomeric amyloidogenic intermediate of a β-structured SH3 domain, which was induced by trifluoroethanol (TFE). The combined biophysical studies showed that the native state SH3 domain is gradually converted to the amyloidogenic intermediate state at TFE concentrations of 20–26% (v/v) and the aggregation-prone state contains substantial amount of the β-sheet conformation (∼30%) with disordered (54%) and some helical characters (16%). Under weaker amyloidogenic conditions of higher TFE concentrations (>40%), the β-sheet structures were gradually changed to helical conformations and the relative content of the helical and β-sheet conformations was highly correlated with the aggregation propensity of the SH3 domain. This indicates that the β-sheet characters of the amyloidogenic states may be critical to the effective amyloid formation.

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