Dataset Information

Characterization of Lipid A Variants by Energy-Resolved Mass Spectrometry: Impact of Acyl Chains.

ABSTRACT: Lipid A molecules consist of a diglucosamine sugar core with a number of appended acyl chains that vary in their length and connectivity. Because of the challenging nature of characterizing these molecules and differentiating between isomeric species, an energy-resolved MS/MS strategy was undertaken to track the fragmentation trends and map genealogies of product ions originating from consecutive cleavages of acyl chains. Generalizations were developed based on the number and locations of the primary and secondary acyl chains as well as variations in preferential cleavages arising from the location of the phosphate groups. Secondary acyl chain cleavage occurs most readily for lipid A species at the 3' position, followed by primary acyl chain fragmentation at both the 3' and 3 positions. In the instances of bisphosphorylated lipid A variants, phosphate loss occurs readily in conjunction with the most favorable primary and secondary acyl chain cleavages. Graphical Abstract ?.

SUBMITTER: Crittenden CM

PROVIDER: S-EPMC5438766 | biostudies-other | 2017 Jun

REPOSITORIES: biostudies-other

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Characterization of Lipid A Variants by Energy-Resolved Mass Spectrometry: Impact of Acyl Chains.

Crittenden Christopher M CM Akin Lucas D LD Morrison Lindsay J LJ Trent M Stephen MS Brodbelt Jennifer S JS

Journal of the American Society for Mass Spectrometry 20161213 6

Lipid A molecules consist of a diglucosamine sugar core with a number of appended acyl chains that vary in their length and connectivity. Because of the challenging nature of characterizing these molecules and differentiating between isomeric species, an energy-resolved MS/MS strategy was undertaken to track the fragmentation trends and map genealogies of product ions originating from consecutive cleavages of acyl chains. Generalizations were developed based on the number and locations of the pr ...[more]

PMID: 27966172

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Project description:Understanding the relationship between protein structure and experimental data is crucial for utilizing experiments to solve biochemical problems and optimizing the use of sparse experimental data for structural interpretation. Tandem mass spectrometry (MS/MS) can be used with a variety of methods to collect structural data for proteins. One example is surface-induced dissociation (SID), which is used to break apart protein complexes (via a surface collision) into intact subcomplexes and can be performed at multiple laboratory frame SID collision energies. These energy-resolved MS/MS experiments have shown that the profile of the breakages depends on the acceleration energy of the collision. It is possible to extract an appearance energy (AE) from energy-resolved mass spectrometry (ERMS) data, which shows the relative intensity of each type of subcomplex as a function of SID acceleration energy. We previously determined that these AE values for specific interfaces correlated with structural features related to interface strength. In this study, we further examined the structural relationships by developing a method to predict the full ERMS plot from the structure, rather than extracting a single value. First, we noted that for proteins with multiple interface types, we could reproduce the correct shapes of breakdown curves, further confirming previous structural hypotheses. Next, we demonstrated that interface size and energy density (measured using Rosetta) correlated with data derived from the ERMS plot (R2 = 0.71). Furthermore, based on this trend, we used native crystal structures to predict ERMS. The majority of predictions resulted in good agreement, and the average root-mean-square error was 0.20 for the 20 complexes in our data set. We also show that if additional information on cleavage as a function of collision energy could be obtained, the accuracy of predictions improved further. Finally, we demonstrated that ERMS prediction results were better for the native than for inaccurate models in 17/20 cases. An application to run this simulation has been developed in Rosetta, which is freely available for use.

Dataset Information

Characterization of Lipid A Variants by Energy-Resolved Mass Spectrometry: Impact of Acyl Chains.

Publications

Characterization of Lipid A Variants by Energy-Resolved Mass Spectrometry: Impact of Acyl Chains.

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