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Protein Amyloid Aggregation pp 115–132Cite as

Characterization of Amyloid Oligomers by Electrospray Ionization-Ion Mobility Spectrometry-Mass Spectrometry (ESI-IMS-MS)

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1345))

Abstract

Soluble oligomers formed during the self-assembly of amyloidogenic peptide and protein species are generally thought to be highly toxic. Consequently, thorough characterization of these species is of much interest in the quest for effective therapeutics and for an enhanced understanding of amyloid fibrillation pathways. The structural characterization of oligomeric species, however, is challenging as they are often transiently and lowly populated, and highly heterogeneous. Electrospray ionization-ion mobility spectrometry-mass spectrometry (ESI-IMS-MS) is a powerful technique which is able to detect individual ion species populated within a complex heterogeneous mixture and characterize them in terms of shape, stoichiometry, ligand binding capability, and relative stability. Herein, we describe the use of ESI-IMS-MS to characterize the size and shape of oligomers of beta-2-microglobulin through use of data calibration and the derivation of models. This enables information about the range of oligomeric species populated en route to amyloid formation and the mode of oligomer growth to be obtained.

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Acknowledgements

CAS is funded by the Biotechnology and Biological Sciences Research Council (BBSRC; grant number BB/H024875/1). The Synapt HDMS mass spectrometer was purchased with funds from the BBSRC’s Research Equipment Initiative (BB/E012558/1). SER’s research is supported by an ERC Advanced grant (322408). The authors would like to thank Dr. Anton Calabrese for critical evaluation of the manuscript.

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Authors and Affiliations

  1. Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, University of Leeds, Leeds, LS2 9JT, UK

    Charlotte A. Scarff & Alison E. Ashcroft

  2. Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, University of Leeds, Astbury Building, Room 10.122a, Leeds, LS2 9JT, UK

    Sheena E. Radford

Authors
  1. Charlotte A. Scarff
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  2. Alison E. Ashcroft
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  3. Sheena E. Radford
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Corresponding authors

Correspondence to Alison E. Ashcroft or Sheena E. Radford .

Editor information

Editors and Affiliations

  1. Weill Cornell Medical College, New York, New York, USA

    David Eliezer

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Scarff, C.A., Ashcroft, A.E., Radford, S.E. (2016). Characterization of Amyloid Oligomers by Electrospray Ionization-Ion Mobility Spectrometry-Mass Spectrometry (ESI-IMS-MS). In: Eliezer, D. (eds) Protein Amyloid Aggregation. Methods in Molecular Biology, vol 1345. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2978-8_8

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  • DOI: https://doi.org/10.1007/978-1-4939-2978-8_8

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2977-1

  • Online ISBN: 978-1-4939-2978-8

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