Expanding the Types of Lipids Amenable to Native Mass Spectrometry of Lipoprotein Complexes

Native mass spectrometry (MS) has become an important tool for the analysis of membrane proteins. Although detergent micelles are the most commonly used method for solubilizing membrane proteins for native MS, nanoscale lipoprotein complexes such as nanodiscs are emerging as a promising complementar...

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Bibliographic Details
Published in:Journal of the American Society for Mass Spectrometry 2019-08, Vol.30 (8), p.1416-1425
Main Authors: Kostelic, Marius M., Ryan, Alex M., Reid, Deseree J., Noun, Jibriel M., Marty, Michael T.
Format: Article
Language:English
Subjects:
Analytical Chemistry
Animals
Bioinformatics
Biotechnology
Cardiolipins - chemistry
Cattle
Chemistry
Chemistry and Materials Science
Cholesterol - chemistry
Focus: Emerging Investigators: Research Article
G(M1) Ganglioside - chemistry
Ionization
Lipid Bilayers - chemistry
Lipids
Lipids - chemistry
Mass Spectrometry
Membrane Proteins - analysis
Micelles
Models, Molecular
Nanostructures - chemistry
Organic Chemistry
Phase stability
Phospholipids
Proteins
Proteomics
Scientific imaging
Spectroscopy
Sterols
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Summary:Native mass spectrometry (MS) has become an important tool for the analysis of membrane proteins. Although detergent micelles are the most commonly used method for solubilizing membrane proteins for native MS, nanoscale lipoprotein complexes such as nanodiscs are emerging as a promising complementary approach because they solubilize membrane proteins in a lipid bilayer environment. However, prior native MS studies of intact nanodiscs have employed only a limited set of phospholipids that are similar in mass. Here, we extend the range of lipids that are amenable to native MS of nanodiscs by combining lipids with masses that are simple integer multiples of each other. Although these lipid combinations create complex distributions, overlap between resonant peak series allows interpretation of nanodisc spectra containing glycolipids, sterols, and cardiolipin. We also investigate the gas-phase stability of nanodiscs with these new lipids towards collisional activation. We observe that negative ionization mode or charge reduction stabilizes nanodiscs and is essential to preserving labile lipids such as sterols. These new approaches to native MS of nanodiscs will enable future studies of membrane proteins embedded in model membranes that more accurately mimic natural bilayers. Graphical Abstract
ISSN:1044-0305
1879-1123
1879-1123
DOI:10.1007/s13361-019-02174-x