Resolving heterogeneous high-mass macromolecular machineries by Orbitrap-based single particle charge detection mass spectrometry
Heck, A. J. R.; Woerner, T. P.; Snijder, J.; Bennett, A. D.; Agbandje-McKenna, M.; Makarov, A.
Show abstract
Here we show that single particle charge-detection mass spectrometry (CD-MS) can be performed on a ubiquitous Orbitrap mass analyser and applied to the analysis of high-mass (megadalton) heterogeneous biomolecular assemblies. We demonstrate that single particle high-mass ions can survive in the Orbitrap for seconds, whereby their measured signal amplitudes scale linearly with charge state over the entire m/z range. Orbitrap based single particle CD-MS can be used to resolve mixed ion populations, accurately predict charge states, and consequently also the mass of the ions. We successfully applied CD-MS to challenging natural and biotherapeutic protein assemblies, such as IgM oligomers, designed protein nano-cages, ribosome particles and intact, empty- and genome-loaded Adeno-associated virus particles. Single particle CD-MS combined with native MS on existing Orbitrap platforms will greatly expand its application, especially in the mass analysis of megadalton heterogeneous biomolecular assemblies.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Quantitative accuracy and precision in multiplexed single-cell proteomics. 97%
- Separation and Characterization of Endogenous Nucleosomes by Native Capillary Zone Electrophoresis - Top-Down Mass Spectrometry (nCZE-TDMS) 97%
- Native Top-Down Proteomics of Endogenous Protein Complexes Enabled by Online Two-Dimensional Liquid Chromatography 97%
Similar papers in this journal
- Automating data analysis for hydrogen/deuterium exchange mass spectrometry using data-independent acquisition methodology 97%
- Single Cell Proteomics Using a Trapped Ion Mobility Time-of-Flight Mass Spectrometer Provides Insight into the Post-translational Modification Landscape of Individual Human Cells 96%
- Trioxane-based MS-cleavable Cross-linking Mass Spectrometry for Profiling Multimeric Interactions of Cellular Networks 96%
Similar papers in this journal
- Inserting Pre-Analytical Chromatographic Priming Runs Significantly Improves Targeted Pathway Proteomics With Sample Multiplexing 97%
- Hybrid Quadrupole Mass Filter Radial Ejection Linear Ion Trap and Intelligent Data Acquisition Enable Highly Multiplex Targeted Proteomics 97%
- Scribe: next-generation library searching for DDA experiments 96%
Similar papers in this journal
- Structural O-Glycoform Heterogeneity of the SARS-CoV-2 Spike Protein Receptor-Binding Domain Revealed by Native Top-Down Mass Spectrometry 96%
- The Holdup Multiplex, an assay for high-throughput measurement of protein-ligand affinity constants using a mass-spectrometry readout 93%
- Ion mobility mass spectrometry unveils global protein conformations in response to conditions that promote and reverse liquid-liquid phase separation 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.