title: Characterization of Amyloid Oligomers by Electrospray Ionization-Ion Mobility Spectrometry-Mass Spectrometry (ESI-IMS-MS).
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.
authors.affiliation: Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, University of Leeds, Leeds, LS2 9JT, UK.
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Scarff
authors.affiliation: Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, University of Leeds, Leeds, LS2 9JT, UK. a.e.ashcroft@leeds.ac.uk.
authors.forename: Alison E
authors.initials: AE
authors.lastname: Ashcroft
authors.affiliation: Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, University of Leeds, Astbury Building, Room 10.122a, Leeds, LS2 9JT, UK. s.e.radford@leeds.ac.uk.
authors.forename: Sheena E
authors.initials: SE
authors.lastname: Radford
mesh_terms: D058227:Amyloidogenic Proteins / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D001613:beta 2-Microglobulin / Q000737:chemistry* / Q000235:genetics
chemical_list: D058227:Amyloidogenic Proteins; D010455:Peptides; D001613:beta 2-Microglobulin
keywords: Amyloid; Ion mobility spectrometry-mass spectrometry; Native mass spectrometry; Oligomerization; Protein aggregation