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MASS SPECTROMETRY

Seeing flying molecular elephants more clearly

Nature Chemistry volume 14, pages 482–483 (2022)Cite this article

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Extending mass spectrometry measurements of biomolecules into the megadalton regime is challenging due to the limited resolving power of currently used mass analysers. Now, using single ion-charge detection Orbitrap mass spectrometry, a mass accuracy of 0.001% has been demonstrated for protein particles larger than 9 MDa.

Native mass spectrometry aims to characterize intact proteins and protein complexes. The development of electrospray ionization mass spectrometry (ESI-MS) by Nobelist John Fenn1, which gave “electrospray wings to molecular elephants” enabled intact proteins to be measured from non-denaturing solutions, conserving the native protein structure2. Native MS is used to probe the composition as well as the ligand binding, structure and function of large biomolecular complexes, including antibodies, multi-subunit functional protein machines and even intact virus capsids (the outer protein shell found on some viruses). However, the MS analysis of large biomolecule assemblies can be inefficient due to suboptimal ion transmission of these large molecules through the mass analyser and ion fragmentation. Furthermore, most mass analysers have a lower mass resolution at higher mass-to-charge ratios (m/z), which would make it near impossible to discern sufficient features in the mass spectra of heterogeneous and complex samples of high molecular mass. To overcome these challenges, single-particle MS approaches have been developed that bypass the need for resolving and deconvoluting multiple mass spectral signals.

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Fig. 1: Orbitrap-based CDMS.

References

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Authors and Affiliations

  1. Australian Proteome Analysis Facility, Macquarie University, New South Wales, Australia

    Muhammad A. Zenaidee

  2. Departments of Chemistry and Biochemistry and Biological Chemistry, UCLA-DOE Institute, and Molecular Biology Institute, University of California-Los Angeles, Los Angeles, CA, USA

    Joseph A. Loo

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  1. Muhammad A. Zenaidee
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  2. Joseph A. Loo
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Correspondence to Muhammad A. Zenaidee or Joseph A. Loo.

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The authors declare no competing interests.

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Zenaidee, M.A., Loo, J.A. Seeing flying molecular elephants more clearly. Nat. Chem. 14, 482–483 (2022). https://doi.org/10.1038/s41557-022-00941-0

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  • DOI: https://doi.org/10.1038/s41557-022-00941-0

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