Characterisation of FXTAS related isolated intranuclear protein inclusions using laser tweezers raman spectroscopy

Tobias J. Moritz, James A Brunberg, Denise M. Krol, Sebastian Wachsmann-Hogiu, Stephen M. Lane, James W Chan

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12 Scopus citations

Abstract

We report the analysis of the vibrational modes of intranuclear protein inclusions isolated from the brain of human subjects with the Fragile X-associated tremor/ataxia syndrome (FXTAS). In this preliminary study, Raman spectra of optically trapped inclusions were measured and analysed to determine protein composition and structure. Our main findings are as follows:(1) ThespectraofproteininclusionsarecharacteristicofH2AandH2Bhistones, whichcorrelatewithpreviousmassspectrometry (MS) studies; (2) Tyrosine is present in its OH form and exposed at the protein surface; (3) Zn and to a lesser extent Cu bound to histidine side chains are detected in the inclusions; (4) The tryptophan side-chain torsion angle is calculated to be 102° (5) Several potential spectroscopic markers for the inclusions of FXTAS are identified. Theseresults show the capability of using laser tweezers Raman spectroscopy to identify protein inclusions in a non-perturbative way and to gain further insight into the pathogenesis and progression of FXTAS in human subjects and in experimental models of this disorder.

Original languageEnglish (US)
Pages (from-to)33-39
Number of pages7
JournalJournal of Raman Spectroscopy
Volume41
Issue number1
DOIs
Publication statusPublished - Jan 2010

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Keywords

  • Fragilex-associated tremor/ataxiasyndrome
  • Intranuclearinclusions
  • Lasertweezers
  • Proteininclusions
  • Ramanspectroscopy

ASJC Scopus subject areas

  • Spectroscopy
  • Materials Science(all)

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