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Updated: Jun 27, 2026

Time-resolved ElectroSpray Ionization Hydrogen-deuterium Exchange Mass Spectrometry for Studying Protein Structure and Dynamics
Published on: April 17, 2017
Stepwise evolution of protein native structure with electrospray into the gas phase, 10(-12) to 10(2) s
Kathrin Breuker1, Fred W McLafferty
1Institute of Organic Chemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 52a, 6020 Innsbruck, Austria.
Abstract:
Mass spectrometry (MS) has been revolutionized by electrospray ionization (ESI), which is sufficiently "gentle" to introduce nonvolatile biomolecules such as proteins and nucleic acids (RNA or DNA) into the gas phase without breaking covalent bonds. Although in some cases noncovalent bonding can be maintained sufficiently for ESI/MS characterization of the solution structure of large protein complexes and native enzyme/substrate binding, the new gaseous environment can ultimately cause dramatic structural alterations. The temporal (picoseconds to minutes) evolution of native protein structure during and after transfer into the gas phase, as proposed here based on a variety of studies, can involve side-chain collapse, unfolding, and refolding into new, non-native structures. Control of individual experimental factors allows optimization for specific research objectives.
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