ArticleAnalytical chemistry2022
Improved Peptide Backbone Fragmentation Is the Primary Advantage of MS-Cleavable Crosslinkers.
Article in Analytical chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- To cleave or not to cleave: a systemic evaluation of DSS versus DSSO for cross-linking mass spectrometry analysis.Molecular systems biology · 2026Article
- Reprogramming the lipid peroxidation product 4-ONE as a chemoselective cleavable crosslinker.Nature communications · 2026Article
- Inherent MS-cleavability of diazirine photo-cross-links enables residue-level structural analysis.Nature communications · 2026Article
- Evaluation of Cleavable Crosslinking for Characterization of Proteoform Structural Differences by Top-Down Mass Spectrometry.International journal of mass spectrometry · 2026Article
- Phosphorylation-dependent tuning of mRNA deadenylation rates.Nature structural & molecular biology · 2026Article
- Developing a new cleavable crosslinker reagent for in-cell crosslinking.Communications chemistry · 2025Article
- Development and Characterization of a Fluorinated MS-Cleavable Cross-Linker for Structural Proteomics.Journal of the American Society for Mass Spectrometry · 2025Article
- Proteome-wide non-cleavable crosslink identification with MS Annika 3.0 reveals the structure of the C. elegans Box C/D complex.Communications chemistry · 2024Article
- PhoXplex: Combining Phospho-enrichable Cross-Linking with Isobaric Labeling for Quantitative Proteome-Wide Mapping of Protein Interfaces.Journal of proteome research · 2024Article
- Evaluating Imide-Based Mass Spectrometry-Cleavable Cross-Linkers for Structural Proteomics Studies.JACS Au · 2024Article
- Characterize direct protein interactions with enrichable, cleavable and latent bioreactive unnatural amino acids.Nature communications · 2024Article
- Higher-Order Structural Organization of the Mitochondrial Proteome Charted by In Situ Cross-Linking Mass Spectrometry.Molecular & cellular proteomics : MCP · 2023Article
- Cleavable Cross-Linkers Redefined by a Novel MSAnalytical chemistry · 2023Article
- All-in-One Pseudo-MSJournal of the American Society for Mass Spectrometry · 2023Article
- New advances in cross-linking mass spectrometry toward structural systems biology.Current opinion in chemical biology · 2023Review
- Discovery and Characterization of an Acid-Labile Serine-Lysine Cross-Link in Antibody High-Molecular-Weight Species Using a Multipronged Mass Spectrometry Approach.Analytical chemistry · 2023Article
- MS Annika 2.0 Identifies Cross-Linked Peptides in MS2-MS3-Based Workflows at High Sensitivity and Specificity.Journal of proteome research · 2023Article
- Article
- Progress toward Proteome-Wide Photo-Cross-Linking to Enable Residue-Level Visualization of Protein Structures and Networks In Vivo.Analytical chemistry · 2023Article
- High-Sensitivity Proteome-Scale Searches for Crosslinked Peptides Using CRIMP 2.0.Analytical chemistry · 2023Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Proteome-wide crosslinking mass spectrometry studies have coincided with the advent of mass spectrometry (MS)-cleavable crosslinkers that can reveal the individual masses of the two crosslinked peptides. However, recently, such studies have also been published with noncleavable crosslinkers, suggesting that MS-cleavability is not essential. We therefore examined in detail the advantages and disadvantages of using the commonly used MS-cleavable crosslinker, disuccinimidyl sulfoxide (DSSO). Indeed, DSSO gave rise to signature peptide fragments with a distinct mass difference (doublet) for nearly all identified crosslinked peptides. Surprisingly, we could show that it was not these peptide masses that proved the main advantage of MS cleavability of the crosslinker, but improved peptide backbone fragmentation which reduces the ambiguity of peptide identifications. This also holds true for another commonly used MS-cleavable crosslinker, DSBU. We show furthermore that the more intricate MS3-based data acquisition approaches lack sensitivity and specificity, causing them to be outperformed by the simpler and faster stepped higher-energy collisional dissociation (HCD) method. This understanding will guide future developments and applications of proteome-wide crosslinking mass spectrometry.
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Registered trials
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.