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An integrated native mass spectrometry and top-down proteomics method that connects sequence to structure and function of macromolecular complexes
Open accessAbstract
Mass spectrometry (MS) has become a crucial technique for the analysis of protein complexes. Native MS has traditionally examined protein subunit arrangements, while proteomics MS has focused on sequence identification. These two techniques are usually performed separately without taking advantage of the synergies between them. Here we describe the development of an integrated native MS and top-down proteomics method using Fourier-transform ion cyclotron resonance (FTICR) to analyse macromolecular protein complexes in a single experiment. We address previous concerns of employing FTICR MS to measure large macromolecular complexes by demonstrating the detection of complexes up to 1.8 MDa, and we demonstrate the efficacy of this technique for direct acquirement of sequence to higher-order structural information with several large complexes. We then summarize the unique functionalities of different activation/dissociation techniques. The platform expands the ability of MS to integrate proteomics and structural biology to provide insights into protein structure, function and regulation.
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“Since CE separations can be performed in aqueous buffers, protein complexes can be separated in their native structures, preserving non-covalent interactions within a protein and between subunits of protein assemblies, prior to MS detection19–21.”
From Recent trends of capillary electrophoresis‐mass spectrometry in proteomics research (2019) · cites this paper as [19]
In the citing paper
“The success of native MS approaches relies on ESI of proteins in a volatile aqueous buffer that preserves native quaternary and tertiary states in the gas phase19,20.”
From Recent trends of capillary electrophoresis‐mass spectrometry in proteomics research (2019) · cites this paper as [19]
In the citing paper
“Native MS provides a proteomics tool that enables identification and characterization of these biomolecular structures and advances the understanding of their biological pathways at the molecular level19,20,35.”
From Recent trends of capillary electrophoresis‐mass spectrometry in proteomics research (2019) · cites this paper as [19]
In the citing paper
“Top-down mass spectrometry (MS)-based proteomics provides a comprehensive analysis of proteoforms to achieve a proteome-wide understanding of protein functions.”
From Nanoproteomics enables proteoform-resolved analysis of low-abundance proteins in human serum (2020) · cites this paper as [2]
In the citing paper
“Today, this is possible using commercially available time-of-flight,33 Orbitrap,34 and Fourier transform ion cyclotron resonance (FTICR)35 instruments.”
From Higher-order structural characterisation of native proteins and complexes by top-down mass spectrometry (2020) · cites this paper as [35]
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Metadata
- Authors
- Li, H., Nguyen, H. H., Ogorzalek Loo, R. R., Campuzano, I. D. G., & Loo, J. A.
- Affiliations
- University of California, Los Angeles (US)
- Amgen (United States) (US)
- Corresponding author
- Li, Huilin
- Loo, Joseph A.
- Venue
- Nature Chemistry
- Published
- 2018-01-01
- Volume
- 10
- Issue
- 2
- Pages
- 139-148
- ISSN
- 1755-4330 (ISSN-L)
- 1755-4349
- PMC
- PMC5784781
- OpenAlex
- W2781755425
- Cited by
- 249
- References
- 65
- Citations by year
- 2026: 20 · 2025: 26 · 2024: 28 · 2023: 29 · 2022: 25 · 2021: 36 · 2020: 33 · 2019: 34 · 2018: 17
- FWCI
- 13.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Energy
- National Institute of General Medical Sciences (R01GM103479)
- National Center for Research Resources (S10RR028893)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- native mass spectrometry, top-down proteomics, protein complexes, macromolecular complexes, FT-ICR mass spectrometry, protein structure, protein sequences, quaternary structure
- MeSH terms
- Models, Molecular, Protein Conformation, Mass Spectrometry, Proteomics, Multiprotein Complexes
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