Studying 18 MDa virus assemblies with native mass spectrometry.
Studying 18 MDa virus assemblies with native mass spectrometry.
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DOI:
10.1002/anie.201210197
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发表时间:
2013-04-02
影响因子:
16.6
通讯作者:
Heck, Albert J. R.
中科院分区:
文献类型:
--
作者:
Snijder, Joost;Rose, Rebecca J.;Veesler, David;Johnson, John E.;Heck, Albert J. R.
Following John Fenn s Nobel Laureate lecture (“Electrospray Wings for Molecular Elephants”),[1] native mass spectrometry (MS) has been developed as a powerful analytical technique to study large noncovalent protein complexes.[2] Using soft nano-electrospray ionization (nESI), these protein complexes can be transferred intact into the gas phase without significant loss of quaternary or tertiary structure. Minor modifications of commercially available MS instruments [3] can greatly improve the transmission of large ions, therefore yielding accurate and precise mass analysis of intact protein complexes. As a result, the stoichiometry of protein complexes can be readily determined in a native MS approach. The study of solution-phase and gas-phase dissociation along with the combination of MS with ion mobility can also yield valuable information on the stability and topology of a protein complex.[4]Native MS has previously been applied to the study of intact viruses and virus capsids.[5] Apart from their role in viral pathogenesis, capsids are interesting because of their potential applications in nanotechnology and medicine as nanocontainers and nanoreactors and as assembly scaffolds.[6] Native MS enabled the study of intact virus capsids in which (nonnative) cargo encapsulation was quantified and capsid assembly was monitored.[7] These previous studies focused on relatively small capsids with Caspar–Klug triangulation numbers of T= 1, 3, and 4, ranging up to 10 MDa in mass. Although the 10 MDa norovirus capsids could be detected with MS, their precise mass could not be determined due to a lack of resolution of individual charge states.[7b] Chargeresolved spectra were limited to particles up to roughly 5 MDa, which was hypothesized to be the upper size limit achievable.
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