title: Differential Mobility Spectrometry-Hydrogen Deuterium Exchange (DMS-HDX) as a Probe of Protein Conformation in Solution.
abstract: Differential mobility spectrometry (DMS) is an ion mobility technique that has been adopted chiefly as a pre-filter for small- to medium-sized analytes (<1 000 Da). With the exception of a handful of studies that employ an analogue of DMS-field asymmetric waveform ion mobility spectroscopy (FAIMS)-the application of DMS to intact biomacromolecules remains largely unexplored. In this work, we employ DMS combined with gas-phase hydrogen deuterium exchange (DMS-HDX) to probe the gas-phase conformations generated from proteins that were initially folded, partially-folded, and unfolded in solution. Our findings indicate that proteins with distinct structural features in solution exhibit unique deuterium uptake profiles as function of their optimal transmission through the DMS. Ultimately we propose that DMS-HDX can, if properly implemented, provide rapid measurements of liquid-phase protein structural stability that could be of use in biopharmaceuticals development. Graphical Abstract ᅟ.
authors.affiliation: Chemistry Department, York University, Toronto, ON, M3J 1P3, Canada.
authors.forename: Shaolong
authors.initials: S
authors.lastname: Zhu
authors.affiliation: SCIEX, 71 Four Valley Drive, Concord, ON, L4K 4V8, Canada.
authors.forename: J Larry
authors.initials: JL
authors.lastname: Campbell
authors.affiliation: SCIEX, 71 Four Valley Drive, Concord, ON, L4K 4V8, Canada.
authors.forename: Igor
authors.initials: I
authors.lastname: Chernushevich
authors.affiliation: SCIEX, 71 Four Valley Drive, Concord, ON, L4K 4V8, Canada.
authors.forename: J C Yves
authors.initials: JC
authors.lastname: Le Blanc
authors.affiliation: Chemistry Department, York University, Toronto, ON, M3J 1P3, Canada. dkwilson@yorku.ca.|Center for Research in Mass Spectrometry, Department of Chemistry, York University, Toronto, ON, M3J 1P3, Canada. dkwilson@yorku.ca.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Wilson
mesh_terms: D003903:Deuterium; D041961:Deuterium Exchange Measurement; D006859:Hydrogen; D011487:Protein Conformation; D013057:Spectrum Analysis
chemical_list: D006859:Hydrogen; D003903:Deuterium
keywords: Cytochrome c; DMS; Differential mobility spectrometry; Gas phase hydrogen deuterium exchange; HDX; Hydrogen deuterium exchange; Ion mobility; Mass spectrometry; Myoglobin; Protein structure; Tau; Tau protein