Despite their importance, structural biology of membrane proteins has lagged behind that of cytosolic proteins. Emerging mass spectrometry techniques, including footprinting and native mass spectrometry, provide information on membrane protein structure that complement established methods. Nanodiscs are nanoscale lipid bilayers encircled by membrane scaffold protein belts that provide a platform for solubilizing membrane proteins. We have utilized native mass spectrometry to study the intact Nanodisc supramolecular complex. Native mass spectrometry measurements of Nanodiscs of different sizes and lipid compositions yield mass distributions in line with predicted values. Interestingly, the presence of anionic lipids does not significantly alter the charge state, presumably due to shielding by residual counter ions. Collision induced dissociation releases the incorporated target membrane protein for tandem mass spectrometry. The ability to introduce intact Nanodiscs into a mass spectrometer provides a unique launch pad for studying membrane protein complexes, protein-lipid interactions, and for top-down investigations on membrane proteins.

Nanodiscs as a launch pad for membrane protein native mass spectrometry

244th National Meeting (2012)

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