Advances in ion mobility spectrometry–mass spectrometry reveal key insights into amyloid assembly

• Published in: Biochimica et biophysica acta 2013-06, Vol.1834 (6), p.1257-1268
• Main Authors: Woods, L.A., Radford, S.E., Ashcroft, A.E.
• Format: Article
• Language: English
• Subjects: Amyloid; Amyloid - chemistry; Amyloid - metabolism; Ion mobility spectrometry; Ions - chemistry; Ligand binding; Mass spectrometry; mixtures; Oligomer; Protein Conformation; Review; Spectrometry, Mass, Electrospray Ionization - methods
• ISSN: 1570-9639; 0006-3002; 1878-1454
• DOI: 10.1016/j.bbapap.2012.10.002

Interfacing ion mobility spectrometry to mass spectrometry (IMS–MS) has enabled mass spectrometric analyses to extend into an extra dimension, providing unrivalled separation and structural characterization of lowly populated species in heterogeneous mixtures. One biological system that has benefitted significantly from such advances is that of amyloid formation. Using IMS–MS, progress has been made into identifying transiently populated monomeric and oligomeric species for a number of different amyloid systems and has led to an enhanced understanding of the mechanism by which small molecules modulate amyloid formation. This review highlights recent advances in this field, which have been accelerated by the commercial availability of IMS–MS instruments. This article is part of a Special Issue entitled: Mass spectrometry in structural biology. [Display omitted] ► IMS–MS provides insights into the mechanism of amyloid formation. ► IMS–MS enables individual conformers of unfolded proteins to be characterized. ► IMS–MS separates and characterizes individual oligomers in a heterogeneous ensemble. ► Ligand binding to specific protein conformers can be detected using IMS–MS.