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Article Dans Une Revue Journal of the American Chemical Society Année : 2023

Native Electrospray Ionization of Multi-Domain Proteins via a Bead Ejection Mechanism

Résumé

Native ion mobility mass spectrometry is potentially useful for the biophysical characterization of proteins, as the electrospray charge state distribution and the collision cross section distribution depend on their solution conformation. We examine here the charging and gas-phase conformation of multi-subunit therapeutic proteins comprising globular subunits tethered by disordered linkers. The charge and collision cross section distributions are multimodal, suggesting several conformations in solution, as confirmed by solution hydrogen/deuterium exchange. The most intriguing question is the ionization mechanism of these structures: a fraction of the population does not follow the charged residue mechanism, but cannot ionize by pure chain ejection either. We deduce that a hybrid mechanism is possible, wherein globular subunits are ejected one at the time from a parent droplet. The charge vs. solvent accessible surface area correlations of denatured and intrinsically disordered proteins are also compatible with this “bead ejection mechanism”, which we propose as a general tenet of biomolecule electrospray.
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Dates et versions

hal-04119433 , version 1 (06-06-2023)

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Nina Khristenko, Frédéric Rosu, Eric Largy, Jérôme Haustant, Cédric Mesmin, et al.. Native Electrospray Ionization of Multi-Domain Proteins via a Bead Ejection Mechanism. Journal of the American Chemical Society, 2023, 145 (1), pp.498 - 506. ⟨10.1021/jacs.2c10762⟩. ⟨hal-04119433⟩
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