ArticleNature communications2024
Dissecting diazirine photo-reaction mechanism for protein residue-specific cross-linking and distance mapping.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Structures of dynamic interactors at native proteasomes by PhIX-MS and cryo-electron microscopy.Molecular cell · 2026Article
- Identifying lipid-protein interactomes with functional lipid probes.Nature protocols · 2026Review
- [Using activity-based protein profiling method to explore the antitumor targets of spiramycin derivatives].Se pu = Chinese journal of chromatography · 2026Article
- Inherent MS-cleavability of diazirine photo-cross-links enables residue-level structural analysis.Nature communications · 2026Article
- Bifunctional Lipid-Protein Cross-linking Efficiency and Reaction Products.Journal of the American Chemical Society · 2026Article
- Natural Product-Derived Activity-Based and Affinity-Based Probes: Tools for Mechanism of Action Studies.Molecules (Basel, Switzerland) · 2026Review
- Unnatural Amino Acid and Emerging Chemistry Approaches to Map RNA-Protein Interactions.Angewandte Chemie (International ed. in English) · 2026Review
- Diazirines Beyond Photoaffinity Labeling: A Comprehensive Overview of Applications in Biological Sciences, Materials Chemistry, and NMR-Spectroscopy.Angewandte Chemie (International ed. in English) · 2026Review
- Towards a universal cross-linking mass spectrometry approach for protein structure analysis with homo-bi-functional photo-activatable cross-linkers.Communications biology · 2025Article
- In-situ cross-linking mass spectrometry reveals compartment-specific proteasomal interactions and structural heterogeneity.Nature communications · 2025Article
- Article
- The Versatility of Diazirines: Properties, Synthetic and Modern Applications.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Review
- Photo-crosslinkers boost structural information from crosslinking mass spectrometry.Current opinion in structural biology · 2025Review
- Optimal Wavelengths and Solvents to Modulate Diazirine Kinetics.ACS omega · 2025Article
- Vegetative and microbial proteins for bioplastics applications - a review in the indian context.RSC advances · 2025Review
- Mapping small molecule-RNA binding sites via Chem-CLIP synergized with capillary electrophoresis and nanopore sequencing.Nucleic acids research · 2025Article
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9 authors.
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Abstract
While photo-cross-linking (PXL) with alkyl diazirines can provide stringent distance restraints and offer insights into protein structures, unambiguous identification of cross-linked residues hinders data interpretation to the same level that has been achieved with chemical cross-linking (CXL). We address this challenge by developing an in-line system with systematic modulation of light intensity and irradiation time, which allows for a quantitative evaluation of diazirine photolysis and photo-reaction mechanism. Our results reveal a two-step pathway with mainly sequential generation of diazo and carbene intermediates. Diazo intermediate preferentially targets buried polar residues, many of which are inaccessible with known CXL probes for their limited reactivity. Moreover, we demonstrate that tuning light intensity and duration enhances selectivity towards polar residues by biasing diazo-mediated cross-linking reactions over carbene ones. This mechanistic dissection unlocks the full potential of PXL, paving the way for accurate distance mapping against protein structures and ultimately, unveiling protein dynamic behaviors.
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