The DOI matches its Crossref record; 141 of the 143 references it cites were found in a registry or an index.
Top Down proteomics: Facts and perspectives
Open accessAbstract
The rise of the "Top Down" method in the field of mass spectrometry-based proteomics has ushered in a new age of promise and challenge for the characterization and identification of proteins. Injecting intact proteins into the mass spectrometer allows for better characterization of post-translational modifications and avoids several of the serious "inference" problems associated with peptide-based proteomics. However, successful implementation of a Top Down approach to endogenous or other biologically relevant samples often requires the use of one or more forms of separation prior to mass spectrometric analysis, which have only begun to mature for whole protein MS. Recent advances in instrumentation have been used in conjunction with new ion fragmentation using photons and electrons that allow for better (and often complete) protein characterization on cases simply not tractable even just a few years ago. Finally, the use of native electrospray mass spectrometry has shown great promise for the identification and characterization of whole protein complexes in the 100 kDa to 1 MDa regime, with prospects for complete compositional analysis for endogenous protein assemblies a viable goal over the coming few years.
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“This approach is well-known for its high-throughput performance; however, critical information about PTMs and subunit protein assemblies (via non-covalent interactions) is generally lost after proteolysis14,31.”
From Recent trends of capillary electrophoresis‐mass spectrometry in proteomics research (2019) · cites this paper as [31]
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Cites
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
LAEMMLI, U. K. (1970) · Nature · doi:10.1038/227680a0 · Cited by 249,961 · cited 1×
“The most common electrophoretic method is SDS-PAGE, in which SDS-coated protein molecules migrate through a polyacrylamide gel matrix in an electric field achieving separation based largely on molecular weight [40].”
MethodSchägger, H., & von Jagow, G. (1987) · Analytical Biochemistry · doi:10.1016/0003-2697(87)90587-2 · Cited by 11,420 · cited 1×
“Using a Tris-tricine [48] variant of the original separation, the authors were able to identify 35 unique proteins from a single GELFrEE separation of HeLa cells.”
MethodMass Spectrometric Sequencing of Proteins from Silver-Stained Polyacrylamide Gels
Shevchenko, A., Wilm, M. S., Vorm, O., & Mann, M. (1996) · Analytical Chemistry · doi:10.1021/ac950914h · Cited by 8,996 · cited 8×
“Strong anion exchange (SAX) coupled to RPLC-MS for intact protein separations has also been reported for the study of E. coli [34].”
MethodInfluentialElectrospray Ionization for Mass Spectrometry of Large Biomolecules
Fenn, J. B., Mann, M., Meng, C. K., Wong, S. F., & Whitehouse, C. M. (1989) · Science · doi:10.1126/science.2675315 · Cited by 7,634
Mass spectrometry-based proteomics
Aebersold, R., & Mann, M. (2003) · Nature · doi:10.1038/nature01511 · Cited by 6,955 · cited 4×
“Proteomic experiments can be used for the annotation and correction of genome sequences, quantitation of protein abundance, detection of posttranslational modifications (PTMs), and identification of protein-protein interactions [2].”
BackgroundMethodInfluentialLaser desorption ionization of proteins with molecular masses exceeding 10,000 daltons.
Karas, M., & Hillenkamp, F. (1988) · Analytical Chemistry · doi:10.1021/ac00171a028 · Cited by 5,145 · cited 7×
“Wall DB, Kachman MT, Gong SY, Hinderer R, Parus S, Misek DE, Hanash SM, Lubman DM. Isoelectric focusing nonporous RP HPLC: A two-dimensional liquid-phase separation method for mapping of cellular proteins with identification using MALDI-TOF mass spectrometry.”
MethodInfluentialWessel, D., & Flügge, U. (1984) · Analytical Biochemistry · doi:10.1016/0003-2697(84)90782-6 · Cited by 3,997 · cited 1×
“The GELFrEE device was first applied to a Top Down study in 2009, utilizing SDS which was then removed using methanol/chloroform/water precipitation [47] prior to online nanoLC-MS [23].”
MethodProtein and polymer analyses up to m/z 100 000 by laser ionization time-of-flight mass spectrometry
Tanaka, K., Waki, H., Ido, Y., Akita, S., Yoshida, Y., Yoshida, T., & Matsuo, T. (1988) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.1290020802 · Cited by 3,005 · cited 7×
“Wall DB, Kachman MT, Gong SY, Hinderer R, Parus S, Misek DE, Hanash SM, Lubman DM. Isoelectric focusing nonporous RP HPLC: A two-dimensional liquid-phase separation method for mapping of cellular proteins with identification using MALDI-TOF mass spectrometry.”
MethodInfluentialPeptide and protein sequence analysis by electron transfer dissociation mass spectrometry
Syka, J. E. P., Coon, J. J., Schroeder, M. J., Shabanowitz, J., & Hunt, D. F. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402700101 · Cited by 2,370
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
Research works printed but not linked: 2
- Cox, 2007, Is proteomics the new genomics?, Cell, 130, 395, 10.1016/j.cell.2007.07.032 · DOI
- Perkins, 1999, Probability-based protein identification by searching sequence databases using mass spectrometry data, Electrophoresis, 20, 3551, 10.1002/(SICI)1522-2683(19991201)20:18<3551::AID-ELPS3551>3.0.CO;2-2 · DOI
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Li, H. (2018) · Science China Life Sciences · doi:10.1007/s11427-018-9390-0
A graph-based filtering method for top-down mass spectral identification
Yang, R., & Zhu, D. (2018) · BMC Genomics · doi:10.1186/s12864-018-5026-x
Baiwir, D., Nanni, P., Müller, S., Smargiasso, N., Morsa, D., Pauw, E. D., & Mazzucchelli, G. (2018) · Springer eBooks · doi:10.1007/978-3-319-69682-9_5 · Cited by 1
Filip, S. K., & Zoidakis, J. (2018) · Wiley eBooks · doi:10.1002/9781119183952.ch6 · Cited by 1
Mass spectrometry approaches in proteomic and metabolomic studies
Rodziewicz, P., Swarcewicz, B., & Chmielewska, K. (2015) · Biotechnologia · doi:10.5114/bta.2014.54794
“Silver staining has higher sensitivty (-1 ng), but narrow dynamic range and low repeatability (Chevallet et al., 2006).”
Editorial for ''advances in OMICs-based disciplines".
Stagljar, I. (2014) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1016/j.bbrc.2014.03.040
Desiderio, C., & Muntiu, A. (2025) · Journal of Chromatography Open · doi:10.1016/j.jcoa.2025.100293
Proteomics in Mycorrhizal and Plant Pathogenic Fungi
Vita, F., & Ghignone, S. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819990-9.00038-x
Novel Analytical Methods for Allergy-Related Studies
Frossard, M. (2020) · doi:10.5075/epfl-thesis-7271
“(49) Total IgE-Abs concentrations above this value may indicate the sensitivity of the patient to one or more allergens.”
BackgroundNew Technologies in Pre- and Postnatal Diagnosis
Laberge, A., Karalis, A., Chakraborty, P., & Samuels, M. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-814823-5.00053-2
2D-DIGE as a Tool in Neuroproteomics
Weiland, F. (2019) · Neuromethods · doi:10.1007/978-1-4939-9662-9_13
Lisacek, F. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-809633-8.20479-2 · Cited by 1
Blindauer, C. (2019) · Clinical and Translational Perspectives on WILSON DISEASE · doi:10.1016/b978-0-12-810532-0.00010-0
Mass Spectrometry-Based Proteomics Analysis of Secreted Proteins
Cudjoe, & Emmanuel, K. (2018) · doi:10.25772/6phr-kx95
“) bonded to silica, and the mobile phase is hydrophilic ([43]).”
BackgroundInfluentialProtein and Post Translational Modification in Asthma
Safaei, A., & Oskouie, A. A. (2018) · Translational bioinformatics · doi:10.1007/978-981-10-8764-6_6
Proteomic Approaches for Diagnostics of Canine and Feline Dementia
Kováčech, B., Žilková, M., Hanes, J., & Škrabana, R. (2017) · Springer eBooks · doi:10.1007/978-3-319-53219-6_7
Middle-down approaches for mass spectrometry-based protein identification and characterization
Srzentić, K. (2016) · Infoscience (Ecole Polytechnique Fédérale de Lausanne) · doi:10.5075/epfl-thesis-6918
Characterization of Intact Therapeutics and Protein Subunits Using CE-MS Platform
Wang, W. (2016) · Springer eBooks · doi:10.1007/978-3-319-46240-0_7
Waas, M., Farris, S. D., Kropp, E. M., Beckman, J. A., Stempien‐Otero, A., Mahr, C., & Gundry, R. L. (2016) · Springer eBooks · doi:10.1007/978-3-319-31828-8_6
Metadata
- Authors
- Catherman, A. D., Skinner, O. S., & Kelleher, N. L.
- Affiliations
- Northwestern University (US)
- Corresponding author
- Kelleher, Neil L.
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 445
- Issue
- 4
- Pages
- 683-693
- ISSN
- 0006-291X (ISSN-L)
- PMC
- PMC4103433
- OpenAlex
- W2070948666
- Cited by
- 507
- References
- 143
- Citations by year
- 2026: 21 · 2025: 32 · 2024: 31 · 2023: 37 · 2022: 48 · 2021: 49 · 2020: 49 · 2019: 46 · 2018: 41 · 2017: 59 · 2016: 38 · 2015: 42 · 2014: 14
- FWCI
- 5.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM067193)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- top-down proteomics, post-translational modification, protein characterization, protein separation, protein complex identification
- MeSH terms
- Amino Acid Sequence, Animals, Chromatography, Liquid, Electrophoresis, Equipment Design, Humans, Molecular Sequence Data, Proteins, Mass Spectrometry, Proteomics
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