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

Part of the Methods in Molecular Biology book series (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.

Key words

Protein aggregation Amyloid Oligomerization Native mass spectrometry Ion mobility spectrometry-mass spectrometry 

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular BiologyUniversity of LeedsLeedsUK
  2. 2.Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular BiologyUniversity of LeedsLeedsUK

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