Profiling of phospholipids and related lipid structures using multidimensional ion mobility spectrometry-mass spectrometry

Trimpin, Sarah; Tan, Bo; Bohrer, Brian C.; O'Dell, David K.; Merenbloom, Samuel I.; Pazos, Mauricio X.; Clemmer, David E.; Walker, J. Michael

doi:10.1016/j.ijms.2008.12.020

Cited by 57 publications

(56 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Double Bond Stereochemistrymentioning

confidence: 99%

“…Indeed, for other classes of molecules, separation of isomers, including chiral discrimination, has been previously demonstrated [39,40]. Recent studies of complex lipids using conventional drift tube ion-mobility indicate that mobility is most strongly correlated with mass and thus tends to separate lipids based on class rather than isomeric variations [40,41]. Shvartsburg et al have shown, however, that differential ion-mobility is capable of resolving sn-positional isomers in diacylglycerols, which augurs well for the future discrimination of other types of lipid isomers [42].…”

Section: Double Bond Stereochemistrymentioning

confidence: 99%

See 1 more Smart Citation

Time to Face the Fats: What Can Mass Spectrometry Reveal about the Structure of Lipids and Their Interactions with Proteins?

Brown

Mitchell

Oakley

et al. 2012

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

Since the 1950s, X-ray crystallography has been the mainstay of structural biology, providing detailed atomic-level structures that continue to revolutionize our understanding of protein function. From recent advances in this discipline, a picture has emerged of intimate and specific interactions between lipids and proteins that has driven renewed interest in the structure of lipids themselves and raised intriguing questions as to the specificity and stoichiometry in lipid-protein complexes. Herein we demonstrate some of the limitations of crystallography in resolving critical structural features of ligated lipids and thus determining how these motifs impact protein binding. As a consequence, mass spectrometry must play an important and complementary role in unraveling the complexities of lipid-protein interactions. We evaluate recent advances and highlight ongoing challenges towards the twin goals of (1) complete structure elucidation of low, abundant, and structurally diverse lipids by mass spectrometry alone, and (2) assignment of stoichiometry and specificity of lipid interactions within protein complexes.Key words: Lipid-protein interactions, Structural biology, Structural lipidomics, Protein mass spectrometry Lipid-Protein Interactions P roteins and lipids, both integral for the function of all biological systems, are chemically distinct. A protein's three-dimensional structure and ultimately its function are defined by peptide-bonded amino acids and subsequent posttranslational modifications. In contrast, lipids are smaller molecules than proteins, but have a larger array of building blocks and linkage chemistries. Because of these inherent chemical differences, the optimal tools for de novo structural characterization differ between proteins and lipids.Lipid-protein interactions are critical for maintaining biological function in the membrane bilayer, the cytosol, and extracellular space. In the membrane, the chemical structures of lipid solvent molecules are important for the correct folding, insertion, structure, and function of membrane proteins. The interactions between enzymes and their respective lipid substrates are critical for correct substrate recognition and catalysis (e.g., lipoxygenase [1]). Additionally, lipid-protein interactions are increasingly being realized as important in maintaining cellular structure (e.g., cytoskeletal anchoring [2]), scaffolding and localization of multi-subunit protein complexes (e.g., associated kinase anchoring protein complexes [3]), and as second messengers in signal transduction (e.g., protein kinase C [4]).

show abstract

Section: Double Bond Stereochemistrymentioning

confidence: 99%

Section: Double Bond Stereochemistrymentioning

confidence: 99%

Time to Face the Fats: What Can Mass Spectrometry Reveal about the Structure of Lipids and Their Interactions with Proteins?

Brown

Mitchell

Oakley

et al. 2012

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

show abstract

“…Using transmission geometry the matrix treated tissue sections were passed free-hand through the focused laser beam in front of the mass spectrometer orifice (Orbitrap Exactive) obtaining a spatial resolution of Ͻ100 m [1]. The objective is to observe proteins from tissue.Ion mobility spectrometry (IMS) MS has many advantages compared with even high-resolution mass spectrometers because of its ability to extend the dynamic range and separate isomeric composition [4][5][6][7]. This is possible because ions are separated in the IMS dimension according to charge and cross-section (size and shape) [8][9][10][11].…”

mentioning

confidence: 99%

Laserspray ionization (LSI) ion mobility spectrometry (IMS) mass spectrometry

Inutan

Trimpin

2010

J. Am. Soc. Mass Spectrom.

Self Cite

111

View full text Add to dashboard Cite

A simple device is described for desolvation of highly charged matrix/analyte clusters produced by laser ablation leading to multiply charged ions that are analyzed by ion mobility spectrometry-mass spectrometry. Thus, for example, highly charged ions of ubiquitin and lysozyme are cleanly separated in the gas phase according to size and mass (shape and molecular weight) as well as charge using Tri-Wave ion mobility technology coupled to mass spectrometry. This contribution confirms the mechanistic argument that desolvation is necessary to produce multiply charged matrix-assisted laser desorption/ionization (MALDI) ions and points to how these ions can be routinely formed on any atmospheric pressure mass spectrometer. (J Am Soc Mass Spectrom 2010, 21, 1260 -1264 -3]. The principle of this ionization method is that the analyte/matrix sample is ablated by the use of a laser operating at atmospheric pressure (AP) and ions are subsequently formed from highly charged matrix/analyte clusters during a desolvation process. The free choice of charge state selection demonstrates the utility of LSI for the analysis of complex mixtures. Singly charged ions similar to those obtained with matrix-assisted laser desorption/ ionization (MALDI) or multiply charged ions similar to those produced by electrospray ionization (ESI) [2] can be selected using LSI. Multiply charged ions are especially beneficial for providing the ability to ionize by laser ablation larger molecules such as proteins and synthetic polymers on high-performance but mass range limited mass spectrometers such as the Orbitrap Exactive [2,3]. Full range mass spectra of bovine insulin were obtained on as little as 40 fmol when applying ion transfer capillary temperatures of ϳ350°C [3].The unique feature of LSI to produce highly charged ions using direct laser ablation of a solid surface enhances fragmentation as was demonstrated by obtaining nearly complete protein sequence coverage of ubiquitin using electron-transfer dissociation (ETD) technology on a LTQ mass spectrometer [3]. Initial laserspray applications demonstrated the ability to produce singly charged lipid ions from mouse brain tissue under ambient conditions [1]. Using transmission geometry the matrix treated tissue sections were passed free-hand through the focused laser beam in front of the mass spectrometer orifice (Orbitrap Exactive) obtaining a spatial resolution of Ͻ100 m [1]. The objective is to observe proteins from tissue.Ion mobility spectrometry (IMS) MS has many advantages compared with even high-resolution mass spectrometers because of its ability to extend the dynamic range and separate isomeric composition [4][5][6][7]. This is possible because ions are separated in the IMS dimension according to charge and cross-section (size and shape) [8][9][10][11]. One key benefit of this solvent-free gas-phase separation by IMS is that when combined with solvent-free sample preparation [12] achieves total solvent-free analysis by MS entirely decoupling ionization, separation, and mass analyses fro...

show abstract

“…Furthermore, with any MS approach, isomeric compounds are not differentiated, even using high-resolution Fourier transform ion cyclotron resonance (FTICR) MS instrumentation, a drawback that is a particular problem in studying the lipidome, drug metabolism, or protein modifications. [6][7][8][9] Previous efforts aimed at developing total solvent-free analysis by MS, 10 involving solvent-free ionization, [11][12][13] and solvent-free separation methodology, 14 have attempted to circumvent these problems. Ion mobility spectrometry (IMS) is a separation method whose most powerful analytical aspect is the ability to separate mixtures composed of isomers.…”

mentioning

confidence: 99%

“…Ion mobility spectrometry (IMS) is a separation method whose most powerful analytical aspect is the ability to separate mixtures composed of isomers. Initial results 14 describe the applications and benefits of IMS-MS for removing decongestion without prior solvent-based separation approaches or time-consuming fragmentation analysis, indicating its possible applicability for analyses in which liquid chromatography (LC) decongestion is not applicable (e.g. tissue imaging).…”

mentioning

confidence: 99%

Field‐free transmission geometry atmospheric pressure matrix‐assisted laser desorption/ionization for rapid analysis of unadulterated tissue samples

Trimpin

Herath

Inutan

et al. 2009

Rapid Comm Mass Spectrometry

Self Cite

108

View full text Add to dashboard Cite

Profiling of phospholipids and related lipid structures using multidimensional ion mobility spectrometry-mass spectrometry

Cited by 57 publications

References 57 publications

Time to Face the Fats: What Can Mass Spectrometry Reveal about the Structure of Lipids and Their Interactions with Proteins?

Time to Face the Fats: What Can Mass Spectrometry Reveal about the Structure of Lipids and Their Interactions with Proteins?

Laserspray ionization (LSI) ion mobility spectrometry (IMS) mass spectrometry

Field‐free transmission geometry atmospheric pressure matrix‐assisted laser desorption/ionization for rapid analysis of unadulterated tissue samples

Contact Info

Product

Resources

About