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Novel insights into protein misfolding diseases revealed by ion mobility-mass spectrometry

Authors

  • Danielle M. Williams,

    1. School of Chemistry and Physics, The University of Adelaide, North Terrace, Adelaide, South Australia 5005, Australia
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  • Tara L. Pukala

    Corresponding author
    1. School of Chemistry and Physics, The University of Adelaide, North Terrace, Adelaide, South Australia 5005, Australia
    • School of Chemistry and Physics The University of Adelaide, North Terrace, Adelaide, SA 5005, Australia.
    Search for more papers by this author

Abstract

Amyloid disorders incorporate a wide range of human diseases arising from the failure of a specific peptide or protein to adopt, or remain in, its native functional conformational state. These pathological conditions, such as Parkinson's disease, Alzheimer's disease and Huntington's disease are highly debilitating, exact enormous costs on both individuals and society, and are predicted to increase in prevalence. Consequently, they form the focus of a topical and rich area of current scientific research. A major goal in attempts to understand and treat protein misfolding diseases is to define the structures and interactions of protein species intermediate between fully folded and aggregated, and extract a description of the aggregation process. This has proven a difficult task due to the inability of traditional structural biology approaches to analyze structurally heterogeneous systems. Continued developments in instrumentation and analytical approaches have seen ion mobility-mass spectrometry (IM-MS) emerge as a complementary approach for protein structure determination, and in some cases, a structural biology tool in its own right. IM-MS is well suited to the study of protein misfolding, and has already yielded significant structural information for selected amyloidogenic systems during the aggregation process. This review describes IM-MS for protein structure investigation, and provides a summary of current research highlighting how this methodology has unequivocally and unprecedentedly provided structural and mechanistic detail pertaining to the oligomerization of a variety of disease related proteins. © 2013 Wiley Periodicals, Inc., Mass Spec Rev 32:169–187, 2013

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