Advances
in mass resolving power for the analysis of viruses by
native mass spectrometry. (a) Native mass spectra of the 4.6-MDa intact
Cowpea chlorotic mottle virus (CCMV) virions and 9.3 MDa Flock House
virus (FHV) acquired with several platforms for native MS. (Top) Mass
spectrum acquired using a quadrupole time-of-flight (QToF) instrument.
A single series of partly resolved charge states can be observed.
(Middle) Spectrum acquired for the sample on an Orbitrap EMR with
extended mass range, displaying clearly baseline resolved ion signals.
(Bottom) Intact FHV analyzed on an QE-UHMR instrument. The native
mass spectrum of FHV, detected at 42 000 m/z shows baseline resolved charge states at a resolution
of approximately 600. (b) Schematic of the Q-Exactive UHMR Orbitrap
mass spectrometer indicating the various ion optic modifications made
to enable the analysis of intact viruses in red. Adapted with permission
from van de Waterbeemd, M.; Snijder, J.; Tsvetkova, I. B.; Dragnea,
B. G.; Cornelissen, J. J.; Heck, A. J. R. 2016 Examining
the Heterogeneous Genome Content of Multipartite Viruses BMV and CCMV
by Native Mass Spectrometry. J. Am. Soc. Mass Spectrom.27(6): 1000–1009 (ref (25)). Copyright 2016 American
Chemical Society. Adapted by permission from Macmillan Publishers
Ltd.: Nat. Methods, van de Waterbeemd, M.; Fort,
K. L.; Boll, D.; Reinhardt-Szyba, M.; Routh, A.; et al. 2017 High-fidelity mass analysis unveils heterogeneity in intact ribosomal
particles. Nat. Methods, pp. 1–7 (ref (30)). Copyright 2017. Fort,
K. L.; Van De Waterbeemd, M.; Boll, D.; Reinhardt-Szyba, M.; Belov,
M. E. et al. 2018 Expanding the structural analysis capabilities
on an Orbitrap-based mass spectrometer for large macromolecular complexes. Analyst. 143(1): 100–105 (ref (31)). Reproduced by permission
of The Royal Society of Chemistry.