Rapid Profiling of Protein Complex Reorganization in Perturbed Systems
(2023) In Journal of Proteome Research 22(5). p.1520-1536- Abstract
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... (More)
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.
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- author
- Bludau, Isabell ; Nicod, Charlotte ; Martelli, Claudia ; Xue, Peng ; Heusel, Moritz LU ; Fossati, Andrea ; Uliana, Federico ; Frommelt, Fabian ; Aebersold, Ruedi and Collins, Ben C.
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- DIA/SWATH, protein complex, protein−protein interactions, quantitative interaction proteomics
- in
- Journal of Proteome Research
- volume
- 22
- issue
- 5
- pages
- 17 pages
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- pmid:37058003
- scopus:85154030077
- ISSN
- 1535-3893
- DOI
- 10.1021/acs.jproteome.3c00125
- language
- English
- LU publication?
- yes
- id
- 1d67e728-d61c-4fe6-ac96-295bb83a3016
- date added to LUP
- 2023-07-18 14:45:25
- date last changed
- 2024-04-19 23:36:28
@article{1d67e728-d61c-4fe6-ac96-295bb83a3016,
abstract = {{<p>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.</p>}},
author = {{Bludau, Isabell and Nicod, Charlotte and Martelli, Claudia and Xue, Peng and Heusel, Moritz and Fossati, Andrea and Uliana, Federico and Frommelt, Fabian and Aebersold, Ruedi and Collins, Ben C.}},
issn = {{1535-3893}},
keywords = {{DIA/SWATH; protein complex; protein−protein interactions; quantitative interaction proteomics}},
language = {{eng}},
number = {{5}},
pages = {{1520--1536}},
publisher = {{The American Chemical Society (ACS)}},
series = {{Journal of Proteome Research}},
title = {{Rapid Profiling of Protein Complex Reorganization in Perturbed Systems}},
url = {{http://dx.doi.org/10.1021/acs.jproteome.3c00125}},
doi = {{10.1021/acs.jproteome.3c00125}},
volume = {{22}},
year = {{2023}},
}