Native mass spectrometry (MS) has emerged as a powerful technique for studying the oligomeric state and interactions of proteins. However, conventional native MS of membrane proteins has relied on detergent micelles, which may distort membrane protein interactions and are unsuitable for assembly of smaller membrane-embedded peptide complexes. We are developing nanodiscs as an alternative membrane mimetic for native MS that provide a native-like lipid bilayer environment with a defined lipid composition. We have discovered that chemical reagents that modulate the ionization conditions allow us to analyze intact nanodiscs with membrane protein and peptide complexes inside. This novel approach allows us to measure the oligomeric state of membrane protein complexes within the intact nanodisc membrane. We are also employing this technique to characterize assemblies of peptides that interact with membranes. Ultimately, we expect this unique combination of nanodiscs and native MS will provide new insights into interactions of biomolecules with and within lipid membranes.

Characterizing oligomerization of biomolecular assemblies within intact membranes using native mass spectrometry and lipoprotein nanodiscs

2019 Fall National Meeting

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