Abstract
Native mass spectrometry (nMS) enables intact non-covalent complexes to be studied in the gas phase. nMS can provide information on composition, stoichiometry, topology, and, when coupled with surface-induced dissociation (SID), subunit connectivity. Here we describe the characterization of protein complexes by nMS and SID. Substructural information obtained using this method is consistent with the solved complex structure, when a structure exists. This provides confidence that the method can also be used to obtain substructural information for unknowns, providing insight into subunit connectivity and arrangements. High-energy SID can also provide information on proteoforms present. Previously SID has been limited to a few in-house modified instruments and here we focus on SID implemented within an in-house-modified Q Exactive UHMR. However, SID is currently commercially available within the Waters Select Series Cyclic IMS instrument. Projects are underway that involve the NIH-funded native MS resource (nativems.osu.edu), instrument vendors, and third-party vendors, with the hope of bringing the technology to more platforms and labs in the near future. Currently, nMS resource staff can perform SID experiments for interested research groups.
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Acknowledgments
We gratefully acknowledge the current and former Wysocki group members who have contributed to the development and understanding of SID. In particular, we would like to acknowledge Zachary VanAernum and Joshua Gilbert for their hard work incorporating SID into the Exactive platforms and optimizing tuning and Benjamin Jones for helpful discussions during the preparation of this protocol. We would like to acknowledge NSF Grants DBI1455654 and DBI0923551 for SID instrument development. We also acknowledge NIH Grant P41GM128577 for the development of an integrated MS-based structural biology workflow and dissemination of SID .
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Harvey, S.R., Ben-Nissan, G., Sharon, M., Wysocki, V.H. (2022). Surface-Induced Dissociation for Protein Complex Characterization. In: Sun, L., Liu, X. (eds) Proteoform Identification. Methods in Molecular Biology, vol 2500. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2325-1_15
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