ArticleJournal of the American Society for Mass Spectrometry2010
Structural characterization of intact proteins is enhanced by prevalent fragmentation pathways rarely observed for peptides.
Article in Journal of the American Society for Mass Spectrometry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- Disambiguation of Product Ion Assignments, Including Internal Fragment Ions from Top-Down Mass Spectrometry, Using Ion Mobility-Aligned Fragmentation (MAF).Analytical chemistry · 2026Article
- Improved Annotation of Internal Fragments via Trapped-Ion Mobility Enhanced Top-Down Sequencing of Protein Ions.Journal of mass spectrometry : JMS · 2025Article
- Panda-UV Unlocks Deeper Protein Characterization with Internal Fragments in Ultraviolet Photodissociation Mass Spectrometry.Analytical chemistry · 2024Article
- Structural Elucidation of Ubiquitin via Gas-Phase Ion/Ion Cross-Linking Reactions Using Sodium-Cationized Reagents Coupled with Infrared Multiphoton Dissociation.Analytical chemistry · 2024Article
- Top-down proteomics.Nature reviews. Methods primers · 2024Article
- Top-down mass spectrometry and assigning internal fragments for determining disulfide bond positions in proteins.The Analyst · 2022Article
- Deciphering combinatorial post-translational modifications by top-down mass spectrometry.Current opinion in chemical biology · 2022Review
- Towards understanding the formation of internal fragments generated by collisionally activated dissociation for top-down mass spectrometry.Analytica chimica acta · 2022Article
- Internal Fragment Ions Disambiguate and Increase Identifications in Top-Down Proteomics.Journal of proteome research · 2021Article
- Increased Single-Spectrum Top-Down Protein Sequence Coverage in Trapping Mass Spectrometers with Chimeric Ion Loading.Analytical chemistry · 2020Article
- Internal Fragments Generated by Electron Ionization Dissociation Enhance Protein Top-Down Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2020Article
- Using 10,000 Fragment Ions to Inform Scoring in Native Top-down Proteomics.Journal of the American Society for Mass Spectrometry · 2020Article
- Top-Down Proteomics of Medicinal Cannabis.Proteomes · 2019Article
- Top-Down Analysis of Proteins in Low Charge States.Journal of the American Society for Mass Spectrometry · 2019Article
- Maximizing Selective Cleavages at Aspartic Acid and Proline Residues for the Identification of Intact Proteins.Journal of the American Society for Mass Spectrometry · 2019Article
- Modulation of Protein Fragmentation Through Carbamylation of Primary Amines.Journal of the American Society for Mass Spectrometry · 2017Article
- Parsing disease-relevant protein modifications from epiphenomena: perspective on the structural basis of SOD1-mediated ALS.Journal of mass spectrometry : JMS · 2017Article
- Defining Gas-Phase Fragmentation Propensities of Intact Proteins During Native Top-Down Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2017Article
- Ion Activation Methods for Peptides and Proteins.Analytical chemistry · 2016Review
- Analyzing internal fragmentation of electrosprayed ubiquitin ions during beam-type collisional dissociation.Journal of the American Society for Mass Spectrometry · 2015Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
While collisionally activated dissociation (CAD) pathways for peptides are well characterized, those of intact proteins are not. We systematically assigned CAD product ions of ubiquitin, myoglobin, and bovine serum albumin generated using high-yield, in-source fragmentation. Assignment of >98% of hundreds of product ions implies that the fragmentation pathways described are representative of the major pathways. Protein dissociation mechanisms were found to be modulated by both source declustering potential and precursor ion charge state. Like peptides, higher charge states of proteins fragmented at lower energies next to Pro, via mobile protons, while lower charge states fragmented at higher energies after Asp and Glu, via localized protons. Unlike peptides, however, predominant fragmentation channels of proteins occurred at intermediate charge states via non-canonical mechanisms and produced extensive internal fragmentation. The non-canonical mechanisms include prominent cleavages C-terminal to Pro and Asn, and N-terminal to Ile, Leu, and Ser; these cleavages, along with internal fragments, led to a 45% increase in sequence coverage, improving the specificity of top-down protein identification. Three applications take advantage of the different mechanisms of protein fragmentation. First, modulation of declustering potential selectively fragments different charge states, allowing the source region to be used as the first stage of a low-resolution tandem mass spectrometer, facilitating pseudo-MS(3) of product ions with known parent charge states. Second, development and integration of automated modulation of ion funnel declustering potential allows users access to a particular fragmentation mechanism, yielding facile cleavage on a liquid chromatography timescale. Third, augmentation of a top-down search engine improved protein characterization.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.