High resolution native Electrospray (ESI) Mass Spectrometry or Native MS has emerged as a standard tool in characterizing the structure and dynamics of biomolecular complexes. It can also provide insights in the stoichiometry and topology of subunits by inducing partial dissociation of the protein complex.
Since 2005 MS Vision has been active in the field of Native ESI Mass Spectrometry and has fulfilled a pioneering role in the development of the technique by developing dedicated high mass mass spectrometry systems. In close collaboration with the group of prof. Albert Heck at Utrecht University (Hecklab), we have gradually and steadily improved the technology for the analysis of intact protein complexes, often non-covalently bound, preserving native conditions in the gas phase.
As a small, dedicated and focused company, we have developed our technology through modification of Waters series Q-Tof and LCT instruments in response to specific user feedback. We moved on to translate what we had learnt to Synapt instruments, yielding excellent high mass performance and turning Synapt instruments into versatile native MS platforms for structural biochemistry.
Why should you consider a high mass upgrade for native MS?
When working with intact proteins, the m/z values can increase because of a number of factors such as higher pH or loss of surface area upon complex formation. When using quadrupole based selection of ions, quadrupole mass filters have a certain maximum for selection of ions (typically assigned as the upper limit for selection. Commonly this is somewhere between 2.000 and 4.000 amu. However, transmission of ions goes down significantly above 3-4 times the upper limit for selection. Thus, for sensitive analysis of agglomerates, non-covalent complexes or native MS in general where m/z values of 6.000 or more are common, a high mass upgrade makes sense for optimal performance.
What a High Mass Native Synapt systems provides to you:
- Extension of the quadrupole m/z range to 32 kDa, enabling efficient transmission and selection of large protein complexes
- Enhanced control over ion source and transfer region conditions, allowing for softer operation for better preservation of fragile proteins, and hotter conditions for enhanced activation of stable complexes
- Enhanced activation and collisional cooling control in the TriWave region, allowing the admission of different gases into the IMS stage so it can either be used for post-activation cooling or Ion Mobility.
- Customized acquisition settings, for best signal-to-noise in real-time monitoring
- Preserving the Ion Mobility capability of the instrument
Applications range from the analysis of antibodies (Mw determination and purity) Antigen-Antibody interaction studies (stochiometry and affinity studies); Antibody PTM analysis (glycosylation, Antibody Drug Conjugates (ADC)); protein-protein and protein-ligand interactions (stochiometry, topology ) and virus capsids (composition, viral drugs development).
Native mass spectrometry is at the core of what we do! We develop and support these systems since the foundation of our company more than 15 years ago. By our own R&D we could build up a unique expertise in high mass and native mass spec and our specialists know the in’s and out’s of high mass MS. In the context of our R&D projects such as SuperMaMa we are continuously striving for further improvements in the field such as increased quadrupol mass ranges. So, expect even further expanded capabilities in the future!
Native mass spectrometry (native MS) literature using MS Vision instruments:
(When possible, the link provides direct access to the PDF file)
- G.K. Shoemaker et al., “Norwalk Virus Assembly ans Stability Monitored by Mass Spectrometry”, Mol. Cell. Prot. (2010), p 1742-51, DOI: 10.1074/mcp.M900620-MCP200
- J. Snijder et al., “Studying 18 MDa Virus Assemblies with Native Mass Spectrometry”, Angew. Comm. (2013)52:4020-23, DOI: 10.1002/anie.201210197
- C. Haupt et al., “Combining Chemical Cross-linking and Mass Spectrometry of Intact Protein Complexes to Study the Architecture of Multi-subunit Protein Assemblies”, J. Vis. Exp. (2017)129:e56747, DOI: 10.3791/56747
- J. Heidemann, B. Krichel, C. Uetrecht, “Native Massenspektrometrie für die Proteinstrukturanalytik”, Biospektrum (2018)24:164-167, DOI: 10.1007/s12268-018-0907-8
- R. Pogan et al., “Norovirus-like VP1 particles exhibit isolate dependent stability profiles”, J. Phys.: Condensed Matter (2018)30:064006, DOI: 10.1088/1361-648X/aaa43b
- M. Kaldmäe et al., “A strategy for the identification or protein architectures directly from ion mobility mass spectrometry data reveals stabilizing subunit interactionsin light harvesting complexes”, Prot. Sci. (2019)28:1024-30, DOI: 10.1002/pro.3609
- I. Bernal et al., “Structural analysis of ligand-bound states of the Salmonella type III secretion system ATPase InvC”, Prot. Sci. (2019)28:1888-1901, DOI: 10.1002/pro.3704
- V.U. Weiss et al., “Virus-like particle size and molecular weight/mass determination applying gas-phaseelectrophoresis (native nES GEMMA)”, Anal. Bioanal. Chem. (2019)411:5951-62, DOI: 10.1007/s00216-019-01998-6
- P. Lill et al., “Towards the molecular architecture of the peroxisomal receptor docking complex”, Proc. Natl. Acad. Sci. USA (2020), DOI: 10.1073/pnas.2009502117
- F. Drepper et al., “A combinatorial native MS and LC-MS/MS approach reveals high intrinsic phosphorylation of human Tau but minimal levels of other key modifications”, J. Biol. Chem. (2020), DOI: 10.1074/jbc.RA120.015882
- R. Anjanappa et al., “Structures of peptide-free and partially loaded MHC class I molecules reveal mechanisms of peptide selections”, Nature Comm. (2020)11:1314, DOI: 10.1038/s41467-020-14862-4
- B. Krichel et al., “Processing of the SARS-CoV pp1a/ab nsp7-10 region”, Biochem J. (2020)477:1009-19, DOI: 10.1042/BCJ20200029
- S. Zoratto et al., “Molecular weight determination of adeno-associate virus serotype 8 virus-like particle either carrying or lacking genome via native nES gas-phase electrophoretic molecular mobility analysis and nESI QRTOF mass spectrometry”, J. Mass Spectrom. (2021)56:e4786, DOI: 10.1002/jms.4786
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