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

Research output: Contribution to journalArticle

12 Citations (Scopus)

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
StatePublished - Jan 2010

Fingerprint

Raman spectroscopy
Proteins
Lasers
Histidine
Tryptophan
Torsional stress
Raman scattering
Brain
Membrane Proteins
Chemical analysis

Keywords

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

ASJC Scopus subject areas

  • Spectroscopy
  • Materials Science(all)

Cite this

Characterisation of FXTAS related isolated intranuclear protein inclusions using laser tweezers raman spectroscopy. / Moritz, Tobias J.; Brunberg, James A; Krol, Denise M.; Wachsmann-Hogiu, Sebastian; Lane, Stephen M.; Chan, James W.

In: Journal of Raman Spectroscopy, Vol. 41, No. 1, 01.2010, p. 33-39.

Research output: Contribution to journalArticle

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