The power of ion mobility-mass spectrometry for structural characterization and the study of conformational dynamics

Lanucara, Francesco; Holman, Stephen W.; Gray, Christopher; Eyers, Patrick A.

doi:10.1038/nchem.1889

Cited by 769 publications

(737 citation statements)

References 158 publications

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“…The average charge state of each component yields an estimate of SASA for the structure in solution, at the moment of transfer to the gas phase [20,21]. Hyphenation with IM measurements adds a further dimension to species separation and offers estimates of the CCS for each detected structure in the gas phase [22][23][24][25]. These techniques conjugate the exceptional analytical power of mass spectrometry with structural description and, therefore, are particularly well suited to the challenges posed by conformational studies on IDPs [23,26,27].…”

Section: Introductionmentioning

confidence: 99%

Molecular Basis for Structural Heterogeneity of an Intrinsically Disordered Protein Bound to a Partner by Combined ESI-IM-MS and Modeling

D’Urzo

Konijnenberg

Rossetti

et al. 2014

J. Am. Soc. Mass Spectrom.

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Abstract. Intrinsically disordered proteins (IDPs) form biologically active complexes that can retain a high degree of conformational disorder, escaping structural characterization by conventional approaches. An example is offered by the complex between the intrinsically disordered N TAIL domain and the phosphoprotein X domain (P XD ) from measles virus (MeV). Here, distinct conformers of the complex are detected by electrospray ionization-mass spectrometry (ESI-MS) and ion mobility (IM) techniques yielding estimates for the solvent-accessible surface area (SASA) in solution and the average collision cross-section (CCS) in the gas phase. Computational modeling of the complex in solution, based on experimental constraints, provides atomic-resolution structural models featuring different levels of compactness. The resulting models indicate high structural heterogeneity. The intermolecular interactions are predominantly hydrophobic, not only in the ordered core of the complex, but also in the dynamic, disordered regions. Electrostatic interactions become involved in the more compact states. This system represents an illustrative example of a hydrophobic complex that could be directly detected in the gas phase by native mass spectrometry. This work represents the first attempt to modeling the entire N TAIL domain bound to P XD at atomic resolution.

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Section: Introductionmentioning

confidence: 99%

Molecular Basis for Structural Heterogeneity of an Intrinsically Disordered Protein Bound to a Partner by Combined ESI-IM-MS and Modeling

D’Urzo

Konijnenberg

Rossetti

et al. 2014

J. Am. Soc. Mass Spectrom.

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“…Over recent times, ion-mobility spectrometry (IMS) has brought new insights into the behavior of gas-phase ions and complexes of small molecules, biomolecules and polymers [1][2][3]. The IMS separation mechanism, which is based on ion charge, size and shape, may facilitate the separation of isomers and recognition of different ion conformations.…”

Section: Introductionmentioning

confidence: 99%

Adduct-ion formation in trapped ion mobility spectrometry as a potential tool for studying molecular structures and conformations

Zietek

Mengerink

Jordens

et al. 2017

Int. J. Ion Mobil. Spec.

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Recent developments in the field of ion mobility spectrometry provide new possibilities to explore and understand gas-phase ion chemistry. In this study, hyphenated trapped ion mobility spectrometry-mass spectrometry (TIMS-MS) was applied to investigate analyte ion mobility as function of adduct ion formation for twelve pharmaceutically relevant molecules, and for tetrahydrocannabinol (THC) and its isomer cannabidiol (CBD). Samples were introduced by direct infusion and ions were generated with positive electrospray ionization (ESI+) observing protonated and sodiated ions. Measurements were performed with and without addition of cesium-, lithium-, silver-and sodium ions to the samples. For the tested compounds, metal adduct ions with the same m/z but with different mobility and collision cross section (CCSs) were observed, indicating different molecular conformations. Formation of analyte dimers was also observed, which could be associated with molecular geometry of the compounds. By optimizing the range and speed of the electric field gradient and ramp, respectively, the separation of THC and CBD was achieved by employing the adduct formation. This study demonstrates that the favorable resolution of TIMS combined with the ability to detect weakly bound counter ions is a valuable means for rapid detection, separation and structural assignment of molecular isomers and analyte conformations.

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“…IMS is now commonly used in structural biology for low-resolution analysis of protein structure, conformational dynamics, and complex topology [2]. Differential mobility spectrometry (DMS) is an IMS approach that has found a niche in ion pre-filtration of small molecules in particular [3,4].…”

Section: Introductionmentioning

confidence: 99%

Differential Mobility Spectrometry-Hydrogen Deuterium Exchange (DMS-HDX) as a Probe of Protein Conformation in Solution

Zhu

Campbell²,

Chernushevich³

et al. 2016

J. Am. Soc. Mass Spectrom.

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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.

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The power of ion mobility-mass spectrometry for structural characterization and the study of conformational dynamics

Cited by 769 publications

References 158 publications

Molecular Basis for Structural Heterogeneity of an Intrinsically Disordered Protein Bound to a Partner by Combined ESI-IM-MS and Modeling

Molecular Basis for Structural Heterogeneity of an Intrinsically Disordered Protein Bound to a Partner by Combined ESI-IM-MS and Modeling

Adduct-ion formation in trapped ion mobility spectrometry as a potential tool for studying molecular structures and conformations

Differential Mobility Spectrometry-Hydrogen Deuterium Exchange (DMS-HDX) as a Probe of Protein Conformation in Solution

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