Rapid profiling of protein complex reorganization in perturbed systems

Isabell Bludau, Charlotte Nicod, Claudia Martelli, Peng Xue, Moritz Heusel, Andrea Fossati, Federico Uliana, Fabian Frommelt, Ruedi Aebersold, Ben C. Collins*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Protein complexes constitute the primary functional modules of cellular activity. To respond to perturbations, complexes undergo changes in their abundance, subunit composition, or state of modification. Understanding the function of biological systems requires global strategies to capture this contextual state information. Methods based on cofractionation paired with mass spectrometry have demonstrated the capability for deep biological insight, but the scope of studies using this approach has been limited by the large measurement time per biological sample and challenges with data analysis. There has been little uptake of this strategy into the broader life science community despite its rich biological information content. We present a rapid integrated experimental and computational workflow to assess the reorganization of protein complexes across multiple cellular states. The workflow combines short gradient chromatography and DIA/SWATH mass spectrometry with a data analysis toolset to quantify changes in a complex organization. We applied the workflow to study the global protein complex rearrangements of THP-1 cells undergoing monocyte to macrophage differentiation and subsequent stimulation of macrophage cells with lipopolysaccharide. We observed substantial proteome reorganization on differentiation and less pronounced changes in macrophage stimulation. We establish our integrated differential pipeline for rapid and state-specific profiling of protein complex organization.

Original languageEnglish
Pages (from-to)1520-1536
Number of pages17
JournalJournal of Proteome Research
Issue number5
Early online date14 Apr 2023
Publication statusPublished - 05 May 2023


  • Article
  • protein complex
  • protein−protein interactions
  • quantitative interaction proteomics


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