Resolving heterogeneous macromolecular assemblies by Orbitrap-based single-particle charge detection mass spectrometry

Tobias P. Wörner, Joost Snijder, Antonette Bennett, Mavis Agbandje-McKenna, Alexander A. Makarov, Albert J.R. Heck*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

We demonstrate single-particle charge detection mass spectrometry on an Orbitrap for the analysis of megadalton biomolecular assemblies. We establish that the signal amplitudes of individual ions scale linearly with their charge, which can be used to resolve mixed ion populations, determine charge states and thus also determine the masses of individual ions. This enables the ultrasensitive analysis of heterogeneous protein assemblies including immunoglobulin oligomers, ribosomes, proteinaceous nanocontainers and genome-packed adeno-associated viruses.

Original languageEnglish
Pages (from-to)395-398
Number of pages4
JournalNature Methods
Volume17
Issue number4
DOIs
Publication statusPublished - Apr 2020

Funding

We greatly appreciate the several collaborators who provided samples to us that we used in the work presented here. We acknowledge the D. Hilvert group at the ETH Zurich for providing the AaLS-neg samples, the J. Schuurman group at Genmab for providing the mutant IgG samples, the S. Rooijakkers group at the Medical Microbiology Department, University Medical Center, Utrecht, in particular P. Aerts and C. Gosselaar-de Haas, for providing the IgM samples, and the A. Routh group at the University of Texas Medical Branch, in particular E. Jaworski, for providing the FHV samples. This work was supported by the Netherlands Organization for Scientific Research through the Spinoza Award (no. SPI.2017.028) to A.J.R.H. J.S. was further supported by the NWO Gravitation project Institute for Chemical Immunology (no. 024.002.009). Additional support came through the European Union Horizon 2020 INFRAIA project Epic-XS (project no. 823839).

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