Unraveling the composition and behavior of heterogeneous lipid nanodiscs by mass spectrometry

Mass spectrometry (MS) has emerged as a powerful tool to study membrane protein complexes and protein-lipid interactions. Because they provide a precisely-defined lipid bilayer environment, lipoprotein Nanodiscs offer a promising cassette for membrane protein MS analysis. However, heterogeneous lipi...

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Main Authors: Hoi, K, Robinson, C, Marty, M
Format: Journal article
Published: American Chemical Society 2016
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author Hoi, K
Robinson, C
Marty, M
author_facet Hoi, K
Robinson, C
Marty, M
author_sort Hoi, K
collection OXFORD
description Mass spectrometry (MS) has emerged as a powerful tool to study membrane protein complexes and protein-lipid interactions. Because they provide a precisely-defined lipid bilayer environment, lipoprotein Nanodiscs offer a promising cassette for membrane protein MS analysis. However, heterogeneous lipids create several potential challenges for native MS: additional spectral complexity, ambiguous assignments, and differing gas-phase behaviors. Here, we present strategies to address these challenges and streamline analysis of heterogeneous-lipid Nanodiscs. We show that using two lipids of similar mass limits the complexity of the spectra in heterogeneous Nanodiscs and that the lipid composition can be determined by using a dual Fourier transform approach to obtain the average lipid mass. Further, the relationship between gas-phase behavior, lipid composition, and instrumental polarity was investigated to determine the effects of lipid head group chemistry on Nanodisc dissociation mechanisms. These results provide unique mechanistic and methodological insights into characterization of complex and heterogeneous systems by mass spectrometry.
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spelling oxford-uuid:3033527a-303c-43d1-bc8b-a99fa6609f232022-03-26T13:00:02ZUnraveling the composition and behavior of heterogeneous lipid nanodiscs by mass spectrometryJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3033527a-303c-43d1-bc8b-a99fa6609f23Symplectic Elements at OxfordAmerican Chemical Society2016Hoi, KRobinson, CMarty, MMass spectrometry (MS) has emerged as a powerful tool to study membrane protein complexes and protein-lipid interactions. Because they provide a precisely-defined lipid bilayer environment, lipoprotein Nanodiscs offer a promising cassette for membrane protein MS analysis. However, heterogeneous lipids create several potential challenges for native MS: additional spectral complexity, ambiguous assignments, and differing gas-phase behaviors. Here, we present strategies to address these challenges and streamline analysis of heterogeneous-lipid Nanodiscs. We show that using two lipids of similar mass limits the complexity of the spectra in heterogeneous Nanodiscs and that the lipid composition can be determined by using a dual Fourier transform approach to obtain the average lipid mass. Further, the relationship between gas-phase behavior, lipid composition, and instrumental polarity was investigated to determine the effects of lipid head group chemistry on Nanodisc dissociation mechanisms. These results provide unique mechanistic and methodological insights into characterization of complex and heterogeneous systems by mass spectrometry.
spellingShingle Hoi, K
Robinson, C
Marty, M
Unraveling the composition and behavior of heterogeneous lipid nanodiscs by mass spectrometry
title Unraveling the composition and behavior of heterogeneous lipid nanodiscs by mass spectrometry
title_full Unraveling the composition and behavior of heterogeneous lipid nanodiscs by mass spectrometry
title_fullStr Unraveling the composition and behavior of heterogeneous lipid nanodiscs by mass spectrometry
title_full_unstemmed Unraveling the composition and behavior of heterogeneous lipid nanodiscs by mass spectrometry
title_short Unraveling the composition and behavior of heterogeneous lipid nanodiscs by mass spectrometry
title_sort unraveling the composition and behavior of heterogeneous lipid nanodiscs by mass spectrometry
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AT robinsonc unravelingthecompositionandbehaviorofheterogeneouslipidnanodiscsbymassspectrometry
AT martym unravelingthecompositionandbehaviorofheterogeneouslipidnanodiscsbymassspectrometry