Advances in ion mobility-mass spectrometry instrumentation and techniques for characterizing structural heterogeneity

Abstract

Over the last decade, the field of ion mobility-mass spectrometry (IM-MS) has experienced dramatic growth in its application toward ion structure characterization. Enabling advances in instrumentation during this time period include improved conformation resolution and ion sensitivity. Such advances have rendered IM-MS a powerful approach for characterizing samples presenting a diverse array of ion structures. The structural heterogeneity that can be interrogated by IM-MS techniques now ranges from samples containing mixtures of small molecules exhibiting a variety of structural types to those containing very large protein complexes and subcomplexes. In addition to this diversity, IM-MS techniques have been used to probe spontaneous and induced structural transformations occurring in solution or the gas phase. To support these measurement efforts, significant advances have been made in theoretical methods aimed at translating IM-MS data into structural information. These efforts have ranged from providing more reliable trial structures for comparison to the experimental measurements to dramatically reducing the time required to calculate collision cross sections for such structures. In this short review, recent advances in developments in IM-MS instrumentation, techniques, and theory are discussed with regard to their implications for characterization of gas- and solution-phase structural heterogeneity.

Native-Like and Denatured Cytochrome c Ions Yield Cation-to-Anion Proton Transfer Reaction Products with Similar Collision Cross-Sections

“…For example, Ω of complexes that contain 18, 40, 60, and 80 copies of the capsid protein of norovirus are consistent with sheet-like intermediates that are capable of forming capsids, rather than assembly-incompetent aggregates [6]. These approaches can also be extended to study unfolded states, intermediates, and other forms of structural heterogeneity [7]. For example, IM spectra of [Pro 13 + 2H] 2+ ions generated from a sample that was transferred from mostly propanol to mostly water exhibit a total of eight features with different Ω whose abundances depend on time since solvent transfer [8].…”

Native mass spectrometry and ion mobility characterize the orange carotenoid protein functional domains

“…Many mass spectrometers are equipped with Ion Mobility (IM) analysis [32, 35], which may have applications in systems such as OCP. In brief, the protein-ion travel time through the drift tube under an applied electric field against the carrier buffer gas is a function of the protein ion’s mass-to-charge ratio, as well as its size and shape (conformation).…”

EM∩IM: software for relating ion mobility mass spectrometry and electron microscopy data

“…A number of different algorithms 9-14 , tailored to specific applications, have been written to calculate the CCS of a given threedimensional structure, allowing the relation of IM measurements to structures derived from X-ray crystallography, NMR spectroscopy, or atomic modelling [15][16][17] An electron density map is typically a three-dimensional grid, with each voxel having a certain density value. In general, such a map is displayed as a volume demarcated by an isodensity surface, which is generated by specifying a contour-level, the lower electron density threshold (!…”

“…While the MS experiment provides a mass measurement, the IM dimension reports on the ability of an ion to traverse a region of low pressure that, depending on the experimental implementation 7, 8 , may be quantified through an orientationally averaged collision cross-section (CCS). The CCS can subsequently be exploited to validate existing atomic coordinates, assess differing candidate structures, or to guide model building directly [1][2][3][4][5][6] .A number of different algorithms 9-14 , tailored to specific applications, have been written to calculate the CCS of a given threedimensional structure, allowing the relation of IM measurements to structures derived from X-ray crystallography, NMR spectroscopy, or atomic modelling [15][16][17] An electron density map is typically a three-dimensional grid, with each voxel having a certain density value. In general, such a map is displayed as a volume demarcated by an isodensity surface, which is generated by specifying a contour-level, the lower electron density threshold (!…”

“…A number of different algorithms [9][10][11][12][13][14] , tailored to specific applications, have been written to calculate the CCS of a given threedimensional structure, allowing the relation of IM measurements to structures derived from X-ray crystallography, NMR spectroscopy, or atomic modelling [15][16][17] . These algorithms are however limited to taking a coordinate file (e.g.…”