title: Deciphering preferential interactions within supramolecular protein complexes: the proteasome case.
abstract: In eukaryotic cells, intracellular protein breakdown is mainly performed by the ubiquitin-proteasome system. Proteasomes are supramolecular protein complexes formed by the association of multiple sub-complexes and interacting proteins. Therefore, they exhibit a very high heterogeneity whose function is still not well understood. Here, using a newly developed method based on the combination of affinity purification and protein correlation profiling associated with high-resolution mass spectrometry, we comprehensively characterized proteasome heterogeneity and identified previously unknown preferential associations within proteasome sub-complexes. In particular, we showed for the first time that the two main proteasome subtypes, standard proteasome and immunoproteasome, interact with a different subset of important regulators. This trend was observed in very diverse human cell types and was confirmed by changing the relative proportions of both 20S proteasome forms using interferon-γ. The new method developed here constitutes an innovative and powerful strategy that could be broadly applied for unraveling the dynamic and heterogeneous nature of other biologically relevant supramolecular protein complexes.
authors.affiliation: CNRS IPBS (Institut de Pharmacologie et de Biologie Structurale), Toulouse, France Université de Toulouse UPS IPBS, Toulouse, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Fabre
authors.affiliation: CNRS IPBS (Institut de Pharmacologie et de Biologie Structurale), Toulouse, France Université de Toulouse UPS IPBS, Toulouse, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lambour
authors.affiliation: CNRS IPBS (Institut de Pharmacologie et de Biologie Structurale), Toulouse, France Université de Toulouse UPS IPBS, Toulouse, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Garrigues
authors.affiliation: CNRS IPBS (Institut de Pharmacologie et de Biologie Structurale), Toulouse, France Université de Toulouse UPS IPBS, Toulouse, France.
authors.forename: François
authors.initials: F
authors.lastname: Amalric
authors.affiliation: Ludwig Institute for Cancer Research, Brussels, Belgium WELBIO (Walloon Excellence in Life Sciences and Biotechnology), Brussels, Belgium de Duve Institute Université catholique de Louvain, Brussels, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vigneron
authors.affiliation: CNRS IPBS (Institut de Pharmacologie et de Biologie Structurale), Toulouse, France Université de Toulouse UPS IPBS, Toulouse, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Menneteau
authors.affiliation: CNRS IPBS (Institut de Pharmacologie et de Biologie Structurale), Toulouse, France Université de Toulouse UPS IPBS, Toulouse, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Stella
authors.affiliation: CNRS IPBS (Institut de Pharmacologie et de Biologie Structurale), Toulouse, France Université de Toulouse UPS IPBS, Toulouse, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Monsarrat
authors.affiliation: Ludwig Institute for Cancer Research, Brussels, Belgium WELBIO (Walloon Excellence in Life Sciences and Biotechnology), Brussels, Belgium de Duve Institute Université catholique de Louvain, Brussels, Belgium.
authors.forename: Benoît
authors.initials: B
authors.lastname: Van den Eynde
authors.affiliation: CNRS IPBS (Institut de Pharmacologie et de Biologie Structurale), Toulouse, France Université de Toulouse UPS IPBS, Toulouse, France Odile.Schiltz@ipbs.fr Marie-Pierre.Bousquet@ipbs.fr.
authors.forename: Odile
authors.initials: O
authors.lastname: Burlet-Schiltz
authors.affiliation: CNRS IPBS (Institut de Pharmacologie et de Biologie Structurale), Toulouse, France Université de Toulouse UPS IPBS, Toulouse, France Odile.Schiltz@ipbs.fr Marie-Pierre.Bousquet@ipbs.fr.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Bousquet-Dubouch
mesh_terms: D045744:Cell Line, Tumor; D002846:Chromatography, Affinity; D002853:Chromatography, Liquid; D020869:Gene Expression Profiling; D057809:HEK293 Cells; D006801:Humans; D013058:Mass Spectrometry; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D040901:Proteomics / Q000379:methods; D053719:Tandem Mass Spectrometry; D020298:U937 Cells
chemical_list: D046988:Proteasome Endopeptidase Complex
keywords: affinity purification; correlation profiling; label‐free quantitative proteomics; mass spectrometry