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Characterisation of FXTAS related isolated intranuclear protein inclusions using laser tweezers Raman spectroscopy
Author(s) -
Moritz Tobias J.,
Brunberg James A.,
Krol Denise M.,
WachsmannHogiu Sebastian,
Lane Stephen M.,
Chan James W.
Publication year - 2010
Publication title -
journal of raman spectroscopy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.748
H-Index - 110
eISSN - 1097-4555
pISSN - 0377-0486
DOI - 10.1002/jrs.2436
Subject(s) - raman spectroscopy , optical tweezers , chemistry , spectroscopy , crystallography , optics , physics , quantum mechanics
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) The spectra of protein inclusions are characteristic of H2A and H2B histones, which correlate with previous mass spectrometry (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. These results 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. Copyright © 2009 John Wiley & Sons, Ltd.