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  • Review Article
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The power of ion mobility-mass spectrometry for structural characterization and the study of conformational dynamics

Nature Chemistry volume 6, pages 281–294 (2014)Cite this article

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Abstract

Mass spectrometry is a vital tool for molecular characterization, and the allied technique of ion mobility is enhancing many areas of (bio)chemical analysis. Strong synergy arises between these two techniques because of their ability to ascertain complementary information about gas-phase ions. Ion mobility separates ions (from small molecules up to megadalton protein complexes) based on their differential mobility through a buffer gas. Ion mobility-mass spectrometry (IM-MS) can thus act as a tool to separate complex mixtures, to resolve ions that may be indistinguishable by mass spectrometry alone, or to determine structural information (for example rotationally averaged cross-sectional area), complementary to more traditional structural approaches. Finally, IM-MS can be used to gain insights into the conformational dynamics of a system, offering a unique means of characterizing flexibility and folding mechanisms. This Review critically describes how IM-MS has been used to enhance various areas of chemical and biophysical analysis.

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Figure 1: Number of peer-reviewed papers published annually (to end of 2013) combining ion mobility and mass spectrometry.
Figure 2: Schematic diagrams of the main types of ion mobility device.
Figure 3: Arrival-time distributions (ATDs) as determined by TWIMS, and structures of the parent drug ondansetron (1) and its isomeric metabolites.
Figure 4: Comparison of experimentally estimated CCS of five protein standards.
Figure 5: Conformational heterogeneity and dissociation of subunit I from ICL12 implies a mechanism for closing the H+ channel.
Figure 6: Polynucleotide structures as determined using a combination of molecular dynamic simulations and experimentally determined ATDs.

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Acknowledgements

We acknowledge the financial support of the Biotechnology and Biological Sciences Research Council (BB/H007113/1, BB/G009058/1, BB/F00561X/1) and the European Commission's Seventh Framework Programme (FP7), which funded GlycoBioM. C.G. is supported by a BBSRC doctoral training grant. Finally, we thank P. Eyers for a critical reading of the review.

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Authors and Affiliations

  1. Department of Biochemistry, Protein Function Group, Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool, L69 7ZB, UK

    Francesco Lanucara, Stephen W. Holman & Claire E. Eyers

  2. Michael Barber Centre for Mass Spectrometry, Manchester Institute of Biotechnology, School of Chemistry, University of Manchester, 131 Princess Street, M1 7DN, Manchester, UK

    Francesco Lanucara, Stephen W. Holman, Christopher J. Gray & Claire E. Eyers

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  1. Francesco Lanucara
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  2. Stephen W. Holman
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F.L., S.W.H. and C.J.G. contributed equally to this paper.

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Correspondence to Claire E. Eyers.

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Lanucara, F., Holman, S., Gray, C. et al. The power of ion mobility-mass spectrometry for structural characterization and the study of conformational dynamics. Nature Chem 6, 281–294 (2014). https://doi.org/10.1038/nchem.1889

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