Magnifying ion mobility spectrometry–mass spectrometry measurements for biomolecular structure studies

Abstract

Ion mobility spectrometry-mass spectrometry (IMS-MS) provides information about the structures of gas-phase ions in the form of a collision cross section (CCS) with a neutral buffer gas. Indicating relative ion size, a CCS value alone is of limited utility. Although such information can be used to propose different conformer types, finer details of structure are not captured. The increased accessibility of IMS-MS measurements with commercial instrumentation in recent years has ballooned its usage in combination with separate measurements to provide enhanced data from which greater structural inferences can be drawn. This short review presents recent outstanding developments in scientific research that employs complementary measurements that when combined with IMS-MS data are used to characterize the structures of a wide range of compounds.

Investigating the interactions of the first 17 amino acid residues of Huntingtin with lipid vesicles using mass spectrometry and molecular dynamics

“…Therefore, no conclusions can be drawn with regard to the degree of membrane‐induced oligomerization. To disentangle the routes of formation for such a heterogenous mixture of oligomeric species is the subject of future, more extensive experiments employing a greater number of lipid systems as well as gas‐phase separations and reactivity studies . This process will also be examined by MD simulations where multiple peptides are examined with the membrane systems.…”

First-Principles Collision Cross Section Measurements of Large Proteins and Protein Complexes

“…Possibly of even greater significance for native MS is the ability to assess protein purity over traditional gel-based approaches . Native ion mobility-mass spectrometry (IM-MS) makes studies of protein structure possible , as well as shows how interactions with metal ions, , small molecules, , protein tags, proteins, and nucleic acids alter protein structure(s). An important feature of IM-MS is the ability to directly measure individual conformers that may comprise a population of gas-phase structures and the rotationally averaged collision cross sections (CCSs) that can be related to conformation and structural dynamics. − Software deconvolution of IM-MS data can allow for previously unresolved isomeric mixtures to be exposed using automated ion mobility deconvolution (AIMD). − When combined with collision-induced unfolding (CIU) and variable-temperature electrospray ionization (vT-ESI), , it is possible to accurately determine gas- and solution-phase stabilities of the ions, respectively, along with conformational changes that occur upon ligand binding and/or changes of the local environment. − …”

“…29 Possibly of even greater significance for native MS is the ability to assess protein purity over traditional gel-based approaches. 30 Native ion mobility-mass spectrometry (IM-MS) makes studies of protein structure possible 31,32 as well as shows how interactions with metal ions, 33,34 small molecules, 35,36 protein tags, 37 proteins, 29 and nucleic acids 38 alter protein structure(s). An important feature of IM-MS is the ability to directly measure individual conformers that may comprise a population of gas-phase structures and the rotationally averaged collision cross sections (CCSs) that can be related to conformation and structural dynamics.…”

ExMS2: An Integrated Solution for Hydrogen–Deuterium Exchange Mass Spectrometry Data Analysis

“…The analysis workflow might be expanded to search also for complex modifications (disulfides, glycosylation), for integrating covalent-labeling or ion mobility spectrometry (IMS) experiments 41 (which could provide additional peptide checks among other advantages), for top-down and targeted structural analysis and for quantification. Last, about the distribution of our software, we expect to make the integrated ExMS2 package available on request.…”