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Updated: Aug 12, 2026

Combining Chemical Cross-linking and Mass Spectrometry of Intact Protein Complexes to Study the Architecture of Multi-subunit Protein Assemblies
Published on: November 28, 2017
Structure-resolved virus-host interactomics by cross-linking mass spectrometry
1Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Virology, Berlin, Germany; Department of Structural Biology, Leibniz-Forschungsinstitut für Molekulare Pharmakologie, Robert-Roessle-Str. 10, 13125, Berlin, Germany.
Cross-linking mass spectrometry (XL-MS) reveals virus-host protein interactions crucial for viral replication and spread. This technique provides structural insights, advancing systems-level structural virology by overcoming current limitations.
Area of Science:
- Virology
- Structural Biology
- Biochemistry
Background:
- Viruses rely on host protein networks for replication, assembly, and spread.
- Understanding virus-host protein interactions is complex due to variability across infection stages, cell types, and species.
- Mechanistic interpretation requires detailed information on structural interfaces and conformational states.
Purpose of the Study:
- To review the advancements and applications of cross-linking mass spectrometry (XL-MS) in studying virus-host protein interactions.
- To highlight XL-MS's role in providing spatial and structural dimensions to interactomics in native systems.
- To discuss the integration of XL-MS with other techniques for a comprehensive understanding of viral mechanisms.
Main Methods:
- Cross-linking mass spectrometry (XL-MS) to map virus-host protein proximity and structure.
- Integration of XL-MS with affinity purification mass spectrometry (AP-MS).
- Complementary use of cryo-electron microscopy (cryo-EM/cryo-ET), quantitative proteomics, genetic perturbation, and structure prediction.
Main Results:
- XL-MS has evolved from analyzing viral protein complexes to mapping virion architecture and infected-cell interactomes with structural resolution.
- XL-MS effectively connects physical proximity data with molecular mechanisms of viral infection.
- The technique offers a powerful approach to study virus-host interactions in native biological systems.
Conclusions:
- XL-MS is a key technology for advancing structural virology and understanding viral pathogenesis.
- Future quantitative and integrative XL-MS workflows hold promise for systems-level structural virology.
- Addressing limitations in sensitivity, chemical coverage, and temporal resolution will further enhance XL-MS capabilities.
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