The key to the function (or malfunction) of a
protein is closely linked to its three-dimensional shape. Ion
mobility mass spectrometry, as a tool for probing molecular shape,
has the potential to play an important role in the study of proteins.
Over the years, mass spectrometry has proven to be a valuable tool in
understanding intrinsic chemical properties. With the emergence
in the past decade of new ionization methods, mass spectrometry can now
be extended as a tool to study biomolecules on a fundamental level.
Our experimental and theoretical
methods allow us to investigate structure, aggregation and energetics
in a variety of protein systems. In addition, we are able to explore
correlations between solution- and gas-phase protein structures.
We are currently investigating proteins involved in several different
neurological diseases. Alzheimer’s disease, Parkinson’s
disease and transmissible spongiform encephalopathies (TSEs) all involve
protein misfolding and subsequent aggregation in the brain. The
proteins associated with each disease are listed below. The conformational
and aggregation aspects involved in these systems make them ideally suited
for study using ion mobility mass spectrometry.
- "Amyloid β-protein monomer structure: A computational
and experimental study" A. Baumketner, S. L. Bernstein, T. Wyttenbach,
G. Bitan, D. B. Teplow, M. T. Bowers, J.-E. Shea Protein Sci., in
- "Amyloid β-protein: Monomer structure and early
aggregation states of Aβ42 and its Pro19 alloform"
S. L. Bernstein, T. Wyttenbach, A. Baumketner, J.-E. Shea, G. Bitan,
D. B. Teplow, M. T. Bowers J.
Am. Chem. Soc. 2005, 127, 2075-2084
- "α-Synuclein: Stable compact and extended monomeric
structures and pH dependence of dimer formation" S. L. Bernstein,
D. Liu, T. Wyttenbach, M. T. Bowers, J. C. Lee, H. B. Gray, J. R. Winkler
Am. Soc. Mass Spectrom. 2004, 15, 1435-1443