Abstract
Nanodiscs are a promising system for studying gas-phase and solution complexes of membrane proteins and lipids. We previously demonstrated that native electrospray ionization allows mass spectral analysis of intact Nanodisc complexes at single lipid resolution. This report details an improved theoretical framework for interpreting and deconvoluting native mass spectra of Nanodisc lipoprotein complexes. In addition to the intrinsic lipid count and charge distributions, Nanodisc mass spectra are significantly shaped by constructive overlap of adjacent charge states at integer multiples of the lipid mass. We describe the mathematical basis for this effect and develop a probability-based algorithm to deconvolute the underlying mass and charge distributions. The probability-based deconvolution algorithm is applied to a series of dimyristoylphosphatidylcholine Nanodisc native mass spectra and used to provide a quantitative picture of the lipid loss in gas-phase fragmentation.
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Acknowledgments
The research was supported by the Photosynthetic Antenna Research Center (PARC), an Energy Frontier Research Center funded by the US Department of Energy, Office of Basic Energy Science (grant no. DE-SC 0001035 to Robert E. Blankenship), National Institute of General Medical Sciences (grant no. 8 P41 GM103422-35 to M.L.G.), National Institute of Health (grant no. R01-GM31756 and R01-GM33775 to S.G.S.), and the NSF (IBDR 0964199 to M.L.G.). M.T.M. was supported by the Robert C. and Carolyn J. Springborn Graduate Fellowship. H.Z. was funded equally by the DOE grant to Professor Robert E. Blankenship and NIGMS grant to M.L.G., and instrumentation was made available from both the DOE and NIGMS grants. The authors thank Don Rempel for helpful discussions.
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Marty, M.T., Zhang, H., Cui, W. et al. Interpretation and Deconvolution of Nanodisc Native Mass Spectra. J. Am. Soc. Mass Spectrom. 25, 269–277 (2014). https://doi.org/10.1007/s13361-013-0782-y
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DOI: https://doi.org/10.1007/s13361-013-0782-y