title: Spatiotemporal variation of mammalian protein complex stoichiometries.
abstract: BACKGROUND
  Recent large-scale studies revealed cell-type specific proteomes. However, protein complexes, the basic functional modules of a cell, have been so far mostly considered as static entities with well-defined structures. The co-expression of their members has not been systematically charted at the protein level.
  
  
  RESULTS
  We used measurements of protein abundance across 11 cell types and five temporal states to analyze the co-expression and the compositional variations of 182 well-characterized protein complexes. We show that although the abundance of protein complex members is generally co-regulated, a considerable fraction of all investigated protein complexes is subject to stoichiometric changes. Compositional variation is most frequently seen in complexes involved in chromatin regulation and cellular transport, and often involves paralog switching as a mechanism for the regulation of complex stoichiometry. We demonstrate that compositional signatures of variable protein complexes have discriminative power beyond individual cell states and can distinguish cancer cells from healthy ones.
  
  
  CONCLUSIONS
  Our work demonstrates that many protein complexes contain variable members that cause distinct stoichometries and functionally fine-tune complexes spatiotemporally. Only a fraction of these compositional variations is mediated by changes in transcription and other mechanisms regulating protein abundance contribute to determine protein complex stoichiometries. Our work highlights the superior power of proteome profiles to study protein complexes and their variants across cell states.
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.|Present address: Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena, Germany.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ori
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.|Present address: Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Murat
authors.initials: M
authors.lastname: Iskar
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Buczak
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Kastritis
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
authors.forename: Luca
authors.initials: L
authors.lastname: Parca
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
authors.forename: Amparo
authors.initials: A
authors.lastname: Andrés-Pons
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.|Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Singer
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany. bork@embl.de.|Max-Delbrück-Centre for Molecular Medicine, Berlin, Germany. bork@embl.de.
authors.forename: Peer
authors.initials: P
authors.lastname: Bork
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany. martin.beck@embl.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Beck
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000235:genetics*; D002843:Chromatin / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008322:Mammals; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000235:genetics; D017434:Protein Structure, Tertiary; D020543:Proteome / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D046912:Multiprotein Complexes; D020543:Proteome
keywords: Cancer; Epigenetic; Paralog; Protein complex; Proteomics; Reprogramming; Stoichiometry; Transport