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Download Hi-Res ImageDownload to MS-PowerPointCite This:Anal. Chem. 2020, 92, 23, 15489-15496
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Enhanced Collision Induced Unfolding and Electron Capture Dissociation of Native-like Protein Ions

  • Varun V. Gadkari
    Varun V. Gadkari
    Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109, United States
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  • Carolina Rojas Ramírez
    Carolina Rojas Ramírez
    Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109, United States
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  • , 
  • Daniel D. Vallejo
    Daniel D. Vallejo
    Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109, United States
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  • Ruwan T. Kurulugama
    Ruwan T. Kurulugama
    Agilent Technologies, 5301 Stevens Creek Blvd, Santa Clara, California 98051, United States
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  • John C. Fjeldsted
    John C. Fjeldsted
    Agilent Technologies, 5301 Stevens Creek Blvd, Santa Clara, California 98051, United States
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  • , and 
  • Brandon T. Ruotolo*
    Brandon T. Ruotolo
    Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109, United States
    *Email: [email protected]. Tel.: 1-734-615-0198. Fax: 1-734-615-3718.
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Cite this: Anal. Chem. 2020, 92, 23, 15489–15496
Publication Date (Web):November 9, 2020
https://doi.org/10.1021/acs.analchem.0c03372
Copyright © 2020 American Chemical Society
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    Abstract

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    Native ion mobility-mass spectrometry (IM-MS) is capable of revealing much that remains unknown within the structural proteome, promising such information on refractory protein targets. Here, we report the development of a unique drift tube IM-MS (DTIM-MS) platform, which combines high-energy source optics for improved collision induced unfolding (CIU) experiments and an electromagnetostatic cell for electron capture dissociation (ECD). We measured a series of high precision collision cross section (CCS) values for protein and protein complex ions ranging from 6–1600 kDa, exhibiting an average relative standard deviation (RSD) of 0.43 ± 0.20%. Furthermore, we compare our CCS results to previously reported DTIM values, finding strong agreement across similarly configured instrumentation (average RSD of 0.82 ± 0.73%), and systematic differences for DTIM CCS values commonly used to calibrate traveling-wave IM separators (−3% average RSD). Our CIU experiments reveal that the modified DTIM-MS instrument described here achieves enhanced levels of ion activation when compared with any previously reported IM-MS platforms, allowing for comprehensive unfolding of large multiprotein complex ions as well as interplatform CIU comparisons. Using our modified DTIM instrument, we studied two protein complexes. The enhanced CIU capabilities enable us to study the gas phase stability of the GroEL 7-mer and 14-mer complexes. Finally, we report CIU-ECD experiments for the alcohol dehydrogenase tetramer, demonstrating improved sequence coverage by combining ECD fragmentation integrated over multiple CIU intermediates. Further improvements for such native top-down sequencing experiments were possible by leveraging IM separation, which enabled us to separate and analyze CID and ECD fragmentation simultaneously.

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.analchem.0c03372.

    • Computationally measured CCS of GroEL complexes, CID and CIU of GroEL complexes, additional CIU comparisons between TWIM and DTIM platforms, IM-ECD supplemental information regarding analysis, collision cross section measurement tables, and IM-ECD fragment count tables (PDF)

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