ArticleProceedings of the National Academy of Sciences of the United States of America2021
Protein interaction landscapes revealed by advanced in vivo cross-linking-mass spectrometry.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed.
- Host-pathogen interactions in tuberculosis: from immunological mechanisms to translational applications.Cell insight · 2026Review
- Advancements and applications of click chemistry in protein labeling and bioconjugation.RSC advances · 2026Review
- To cleave or not to cleave: a systemic evaluation of DSS versus DSSO for cross-linking mass spectrometry analysis.Molecular systems biology · 2026Article
- Quantitative interactome mapping of skeletal muscle insulin resistance.Molecular systems biology · 2026Article
- Mapping the architecture of protein complexes inProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Systematic Targeting of Protein Complexes with Molecular COUPLrs.Cancer discovery · 2026Article
- DirectContacts2: a wiring diagram of human physical protein interactions.Nature communications · 2026Article
- Protocol for analyzing protein interactomes under starvation in fission yeast using in vivo cross-linking.STAR protocols · 2026Article
- Investigating the relationship between ATP synthase and the TCA cycle by crosslinking mass spectrometry.Nature communications · 2026Article
- A 15-layer multi-omics analysis of gastric cancer ecotypes provides therapeutic insights.Cell reports. Medicine · 2026Article
- Strategies for constructing context-specific protein-protein interaction networks.Briefings in bioinformatics · 2026Review
- Lactate derived from macrophages drives skin dermal fibroblasts phenotypic remodeling via MCT1-primed histone H3 lysine 23 lactylation in hypertrophic scar.Nature communications · 2026Article
- Optimized In-Solution and Gas-Phase Chemistry Enables High-Efficiency Interactome Mapping by DSBSO-Based Cross-Linking Mass Spectrometry.Angewandte Chemie (International ed. in English) · 2026Article
- Cysteine-enabled cleavability to advance cross-linking mass spectrometry for global analysis of endogenous protein-protein interactions.Nature communications · 2025Article
- In-situ cross-linking mass spectrometry reveals compartment-specific proteasomal interactions and structural heterogeneity.Nature communications · 2025Article
- Breaking barriers in crosslinking mass spectrometry with enhanced throughput and sensitivity using Orbitrap Astral.Nature communications · 2025Article
- Click-linking: a cell-compatible protein crosslinking method based on click chemistry.Nature communications · 2025Article
- Integrating diverse experimental information to assist protein complex structure prediction by GRASP.Nature methods · 2025Article
- Mapping amBio · 2025Article
- State-of-the-Art and Future Directions in Structural Proteomics.Molecular & cellular proteomics : MCP · 2025Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Defining protein-protein interactions (PPIs) in their native environment is crucial to understanding protein structure and function. Cross-linking-mass spectrometry (XL-MS) has proven effective in capturing PPIs in living cells; however, the proteome coverage remains limited. Here, we have developed a robust in vivo XL-MS platform to facilitate in-depth PPI mapping by integrating a multifunctional MS-cleavable cross-linker with sample preparation strategies and high-resolution MS. The advancement of click chemistry-based enrichment significantly enhanced the detection of cross-linked peptides for proteome-wide analyses. This platform enabled the identification of 13,904 unique lysine-lysine linkages from in vivo cross-linked HEK 293 cells, permitting construction of the largest in vivo PPI network to date, comprising 6,439 interactions among 2,484 proteins. These results allowed us to generate a highly detailed yet panoramic portrait of human interactomes associated with diverse cellular pathways. The strategy presented here signifies a technological advancement for in vivo PPI mapping at the systems level and can be generalized for charting protein interaction landscapes in any organisms.
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