The DOI matches its Crossref record; 65 of the 65 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Fourier transform ion cyclotron resonance mass spectrometry: A primer
Marshall, A. G., Hendrickson, C. L., & Jackson, G. S. (1998) · Mass Spectrometry Reviews · doi:10.1002/(sici)1098-2787(1998)17:1 · Cited by 2,045
XX. On the equilibrium of liquid conducting masses charged with electricity
Rayleigh, L. (1882) · The London Edinburgh and Dublin Philosophical Magazine and Journal of Science · doi:10.1080/14786448208628425 · Cited by 1,873
Proteoform: a single term describing protein complexity
The Consortium for Top Down Proteomics, Smith, L. M., & Kelleher, N. L. (2013) · Nature Methods · doi:10.1038/nmeth.2369 · Cited by 1,528
Current Protocols in Protein Science
(2018) · Current Protocols in Protein Science · doi:10.1002/(issn)1934-3663 · Cited by 1,191
Hydrophobicity of Amino Acid Residues in Globular Proteins
Rose, G. D., Geselowitz, A., Lesser, G. J., Lee, R., & Zehfus, M. H. (1985) · Science · doi:10.1126/science.4023714 · Cited by 1,176
Native mass spectrometry: a bridge between interactomics and structural biology
Heck, A. J. R. (2008) · Nature Methods · doi:10.1038/nmeth.1265 · Cited by 766
Three-dimensional structure of β-galactosidase from E. coli.
Jacobson, R. H., Zhang, X. ‐., DuBose, R. F., & Matthews, B. W. (1994) · Nature · doi:10.1038/369761a0 · Cited by 600
Current Protocols in Protein Science
(2001) · John Wiley & Sons, Inc. eBooks · doi:10.1002/0471140864 · Cited by 600
Decoding protein modifications using top-down mass spectrometry
Siuti, N., & Kelleher, N. L. (2007) · Nature Methods · doi:10.1038/nmeth1097 · Cited by 503
Protein Complexes in the Gas Phase: Technology for Structural Genomics and Proteomics
Benesch, J. L. P., Ruotolo, B. T., Simmons, D. A., & Robinson, C. V. (2007) · Chemical Reviews · doi:10.1021/cr068289b · Cited by 420
High-sensitivity Orbitrap mass analysis of intact macromolecular assemblies
Rose, R. J., Damoc, E., Denisov, E., Makarov, A., & Heck, A. J. R. (2012) · Nature Methods · doi:10.1038/nmeth.2208 · Cited by 392
Electron-capture dissociation tandem mass spectrometry
Zubarev, R. A. (2003) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2003.12.002 · Cited by 362
Activated Ion Electron Capture Dissociation for Mass Spectral Sequencing of Larger (42 kDa) Proteins
Horn, D. M., Ge, Y., & McLafferty, F. W. (2000) · Analytical Chemistry · doi:10.1021/ac000494i · Cited by 334
Glycogen phosphorylase: control by phosphorylation and allosteric effectors
Johnson, L. N. (1992) · The FASEB Journal · doi:10.1096/fasebj.6.6.1544539 · Cited by 323
Cleavage N-Terminal to Proline: Analysis of a Database of Peptide Tandem Mass Spectra
Breci, L. A., Tabb, D. L., Yates, J. R., & Wysocki, V. H. (2003) · Analytical Chemistry · doi:10.1021/ac026359i · Cited by 307
Ion Activation Methods for Peptides and Proteins
Brodbelt, J. S. (2015) · Analytical Chemistry · doi:10.1021/acs.analchem.5b04563 · Cited by 259
High-resolution mass spectrometry of small molecules bound to membrane proteins
Gault, J., Donlan, J. A. C., Liko, I., Hopper, J. T. S., Gupta, K., Housden, N. G., Struwe, W. B., Marty, M. T., Mize, T. H., Bechara, C., et al. (2016) · Nature Methods · doi:10.1038/nmeth.3771 · Cited by 243
Structural mechanism for glycogen phosphorylase control by phosphorylation and AMP
Barford, D., Hu, S. H., & Johnson, L. N. (1991) · Journal of Molecular Biology · doi:10.1016/0022-2836(91)90887-c · Cited by 242
Top-Down ESI-ECD-FT-ICR Mass Spectrometry Localizes Noncovalent Protein-Ligand Binding Sites
Xie, Y., Zhang, J., Yin, S., & Loo, J. A. (2006) · Journal of the American Chemical Society · doi:10.1021/ja063197p · Cited by 201
Self-citationStudying 18 MDa Virus Assemblies with Native Mass Spectrometry
Snijder, J., Rose, R., Veesler, D., Johnson, J. E., & Heck, A. J. R. (2013) · Angewandte Chemie International Edition · doi:10.1002/anie.201210197 · Cited by 191
Detection of the Intact GroEL Chaperonin Assembly by Mass Spectrometry
Rostom, A. A., & Robinson, C. V. (1999) · Journal of the American Chemical Society · doi:10.1021/ja990238r · Cited by 179
Belov, M. E., Damoc, E., Denisov, E., Compton, P. D., Horning, S., Makarov, A. A., & Kelleher, N. L. (2013) · Analytical Chemistry · doi:10.1021/ac4029328 · Cited by 175
The structure of E. coli β-galactosidase
Matthews, B. W. (2005) · Comptes Rendus Biologies · doi:10.1016/j.crvi.2005.03.006 · Cited by 173
Snijder, J., van de Waterbeemd, M., Damoc, E., Denisov, E., Grinfeld, D., Bennett, A., Agbandje-McKenna, M., Makarov, A., & Heck, A. J. R. (2014) · Journal of the American Chemical Society · doi:10.1021/ja502616y · Cited by 168
High-fidelity mass analysis unveils heterogeneity in intact ribosomal particles
van de Waterbeemd, M., Fort, K. L., Boll, D., Reinhardt-Szyba, M., Routh, A., Makarov, A., & Heck, A. J. R. (2017) · Nature Methods · doi:10.1038/nmeth.4147 · Cited by 168
Shi, Y., Fernández-Martı́nez, J., Tjioe, E., Pellarin, R., Kim, S. J., Williams, R., Schneidman‐Duhovny, D., Šali, A., Rout, M. P., & Chait, B. T. (2014) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m114.041673 · Cited by 166
Zhang, H., Cui, W., Wen, J., Blankenship, R. E., & Gross, M. L. (2011) · Analytical Chemistry · doi:10.1021/ac200695d · Cited by 163
Infrared multiphoton dissociation in quadrupole ion traps
Brodbelt, J. S., & Wilson, J. J. (2009) · Mass Spectrometry Reviews · doi:10.1002/mas.20216 · Cited by 155
Mass spectrometry supported determination of protein complex structure
Walzthoeni, T., Leitner, A., Stengel, F., & Aebersold, R. (2013) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2013.02.008 · Cited by 146
Rosati, S., Yang, Y., Barendregt, A., & Heck, A. J. R. (2014) · Nature Protocols · doi:10.1038/nprot.2014.057 · Cited by 138
Enhanced top-down characterization of histone post-translational modifications
Tian, Z., Tolić, N., Zhao, R., Moore, R., Hengel, S. M., Robinson, E. W., Stenoien, D. L., Wu, S., Smith, R. D., & Paša‐Tolić, L. (2012) · Genome biology · doi:10.1186/gb-2012-13-10-r86 · Cited by 126
A tale of two tails: why are terminal residues of proteins exposed?
Jacob, E., & Unger, R. (2007) · Bioinformatics · doi:10.1093/bioinformatics/btl318 · Cited by 123
Tsaprailis, G., Somogyi, Á., Николаев, Е. Н., & Wysocki, V. H. (2000) · International Journal of Mass Spectrometry · doi:10.1016/s1387-3806(99)00221-3 · Cited by 121
Li, H., Wolff, J. J., Orden, S. L. V., & Loo, J. A. (2013) · Analytical Chemistry · doi:10.1021/ac4033214 · Cited by 119
Self-citationDetection of intact megaDalton protein assemblies of vanillyl‐alcohol oxidase by mass spectrometry
van Berkel, W. J. H., van den Heuvel, R. H. H., Versluis, C., & Heck, A. J. R. (2000) · Protein Science · doi:10.1110/ps.9.3.435 · Cited by 116
Characterising electrosprayed biomolecules using tandem-MS—the noncovalent GroEL chaperonin assembly
Sobott, F., & Robinson, C. V. (2004) · International Journal of Mass Spectrometry · doi:10.1016/j.ijms.2004.05.010 · Cited by 112
The emergence of top-down proteomics in clinical research
Savaryn, J. P., Catherman, A. D., Thomas, P. M., Abecassis, M. M., & Kelleher, N. L. (2013) · Genome Medicine · doi:10.1186/gm457 · Cited by 109
Untangling the glutamate dehydrogenase allosteric nightmare
Smith, T. J., & Stanley, C. A. (2008) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2008.07.007 · Cited by 109
Karabacak, M., Li, L., Tiwari, A., Hayward, L. J., Hong, P., Easterling, M. L., & Agar, J. N. (2008) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m800099-mcp200 · Cited by 95
Dyachenko, A., Wang, G., Belov, M., Makarov, A., de Jong, R. N., van den Bremer, E. T. J., Parren, P. W. H. I., & Heck, A. J. R. (2015) · Analytical Chemistry · doi:10.1021/acs.analchem.5b00788 · Cited by 93
How far can we go with structural mass spectrometry of protein complexes?
Sharon, M. (2010) · Journal of the American Society for Mass Spectrometry · doi:10.1016/j.jasms.2009.12.017 · Cited by 93
Banerjee, S., Schmidt, T. H., Fang, J., Stanley, C. A., & Smith, T. J. (2003) · Biochemistry · doi:10.1021/bi0206917 · Cited by 92
Evaluation of the Compact High-Field Orbitrap for Top-Down Proteomics of Human Cells
Ahlf, D. R., Compton, P. D., Tran, J. C., Early, B. P., Thomas, P. M., & Kelleher, N. L. (2012) · Journal of Proteome Research · doi:10.1021/pr3004216 · Cited by 89
Proteins, Lipids, and Water in the Gas Phase
van der Spoel, D., Marklund, E. G., Larsson, D. S. D., & Caleman, C. (2010) · Macromolecular Bioscience · doi:10.1002/mabi.201000291 · Cited by 88
Lermyte, F., Konijnenberg, A., Williams, J. P., Brown, J. M., Valkenborg, D., & Sobott, F. (2014) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-013-0798-3 · Cited by 87
Current limitations in native mass spectrometry based structural biology
van Duijn, E. (2010) · Journal of the American Society for Mass Spectrometry · doi:10.1016/j.jasms.2009.12.010 · Cited by 87
Li, H., Wongkongkathep, P., Orden, S. L. V., Loo, R. R. O., & Loo, J. A. (2014) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-014-0928-6 · Cited by 75
Self-citationHaverland, N. A., Skinner, O. S., Fellers, R. T., Tariq, A., Early, B. P., LeDuc, R. D., Fornelli, L., Compton, P. D., & Kelleher, N. L. (2017) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-017-1635-x · Cited by 69
Li, H., Sheng, Y., McGee, W. M., Cammarata, M. B., Holden, D. D., & Loo, J. A. (2017) · Analytical Chemistry · doi:10.1021/acs.analchem.6b02377 · Cited by 63
Self-citationGas-phase metalloprotein complexes interrogated by ion mobility-mass spectrometry
Faull, P. A., Korkeila, K. E., Kalapothakis, J. M. D., Gray, A., McCullough, B. J., & Barran, P. E. (2009) · International Journal of Mass Spectrometry · doi:10.1016/j.ijms.2009.02.024 · Cited by 56
Native mass spectrometry of photosynthetic pigment–protein complexes
Zhang, H., Cui, W., Gross, M. L., & Blankenship, R. E. (2013) · FEBS Letters · doi:10.1016/j.febslet.2013.01.005 · Cited by 54
Durbin, K. R., Skinner, O. S., Fellers, R. T., & Kelleher, N. L. (2015) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-015-1078-1 · Cited by 52
Li, H., Lin, T., Orden, S. L. V., Zhao, Y., Barrow, M. P., Pizarro, A. M., Qi, Y., Sadler, P. J., & O’Connor, P. B. (2011) · Analytical Chemistry · doi:10.1021/ac202267g · Cited by 51
Self-citationElectron Capture Dissociation as Structural Probe for Noncovalent Gas-Phase Protein Assemblies
Geels, R. B. J., van der Vies, S. M., Heck, A. J. R., & Heeren, R. M. A. (2006) · Analytical Chemistry · doi:10.1021/ac060960p · Cited by 49
Detection of mass 16241 ions by Fourier-transform mass spectrometry
Castro, M. E., Russell, D. H., Amster, I. J., & McLafferty, F. W. (1986) · Analytical Chemistry · doi:10.1021/ac00293a049 · Cited by 44
Ma, X., Zhou, M., & Wysocki, V. H. (2014) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-013-0790-y · Cited by 39
Top‐down tandem mass spectrometry on RN ase A and B using a Q h/ FT ‐ ICR hybrid mass spectrometer
Bourgoin‐Voillard, S., Leymarie, N., & Costello, C. E. (2014) · PROTEOMICS · doi:10.1002/pmic.201300433 · Cited by 39
Schennach, M., & Breuker, K. (2013) · Angewandte Chemie International Edition · doi:10.1002/anie.201306838 · Cited by 37
Top-down MS for rapid methionine oxidation site assignment in filgrastim
Holzmann, J., Hausberger, A., Rupprechter, A., & Toll, H. (2013) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-013-7138-0 · Cited by 32
Cui, W., Zhang, H., Blankenship, R. E., & Gross, M. L. (2015) · Protein Science · doi:10.1002/pro.2712 · Cited by 29
Probing Protein Structure and Folding in the Gas Phase by Electron Capture Dissociation
Schennach, M., & Breuker, K. (2015) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-015-1088-z · Cited by 23
Nanospray Ion Mobility Mass Spectrometry of Selected High Mass Species
Campuzano, I. D. G., & Giles, K. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-319-6_5 · Cited by 21
Self-citationNanoproteomics :methods and protocols
Toms, S. A., & Weil, R. J. (2011) · Humana Press eBooks · Cited by 6
The structural basis of proteolytic activation of bovine glutamate dehydrogenase
Carrigan, J. B., & Engel, P. C. (2008) · Protein Science · doi:10.1110/ps.034785.108 · Cited by 4
Protein Complexes: Breaking Up Is Hard to Do Well
Loo, R. R. O., & Loo, J. A. (2013) · Structure · doi:10.1016/j.str.2013.07.013 · Cited by 1
Self-citation
Cited by
Sorted by citations
High-Resolution Native Mass Spectrometry
Tamara, S., den Boer, M. A., & Heck, A. J. R. (2022) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00212 · Cited by 511
Ultraviolet Photodissociation Mass Spectrometry for Analysis of Biological Molecules
Brodbelt, J. S., Morrison, L. J., & Santos, I. C. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.9b00440 · Cited by 302
Novel Strategies to Address the Challenges in Top-Down Proteomics
Melby, J. A., Roberts, D. S., Larson, E. J., Brown, K. A., Bayne, E. F., Jin, S., & Ge, Y. (2021) · Journal of the American Society for Mass Spectrometry · doi:10.1021/jasms.1c00099 · Cited by 201
Protein–Small Molecule Interactions in Native Mass Spectrometry
Bennett, J. L., Nguyen, G. T. H., & Donald, W. A. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00293 · Cited by 161
Roberts, D. S., Loo, J. A., Tsybin, Y. O., Liu, X., Wu, S., Chamot-Rooke, J., Agar, J. N., Paša-Tolić, L., Smith, L. M., & Ge, Y. (2024) · Nature Reviews Methods Primers · doi:10.1038/s43586-024-00318-2 · Cited by 161
Self-citation
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
