title: Functional organization of the yeast proteome by systematic analysis of protein complexes.
abstract: Most cellular processes are carried out by multiprotein complexes. The identification and analysis of their components provides insight into how the ensemble of expressed proteins (proteome) is organized into functional units. We used tandem-affinity purification (TAP) and mass spectrometry in a large-scale approach to characterize multiprotein complexes in Saccharomyces cerevisiae. We processed 1,739 genes, including 1,143 human orthologues of relevance to human biology, and purified 589 protein assemblies. Bioinformatic analysis of these assemblies defined 232 distinct multiprotein complexes and proposed new cellular roles for 344 proteins, including 231 proteins with no previous functional annotation. Comparison of yeast and human complexes showed that conservation across species extends from single proteins to their molecular environment. Our analysis provides an outline of the eukaryotic proteome as a network of protein complexes at a level of organization beyond binary interactions. This higher-order map contains fundamental biological information and offers the context for a more reasoned and informed approach to drug discovery.
authors.affiliation: Cellzome AG, Meyerhofstrasse 1, 69117 Heidelberg, Germany. anne-claude.gavin@cellzome.com
authors.forename: Anne-Claude
authors.initials: AC
authors.lastname: Gavin
authors.forename: Markus
authors.initials: M
authors.lastname: Bösche
authors.forename: Roland
authors.initials: R
authors.lastname: Krause
authors.forename: Paola
authors.initials: P
authors.lastname: Grandi
authors.forename: Martina
authors.initials: M
authors.lastname: Marzioch
authors.forename: Andreas
authors.initials: A
authors.lastname: Bauer
authors.forename: Jörg
authors.initials: J
authors.lastname: Schultz
authors.forename: Jens M
authors.initials: JM
authors.lastname: Rick
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Michon
authors.forename: Cristina-Maria
authors.initials: CM
authors.lastname: Cruciat
authors.forename: Marita
authors.initials: M
authors.lastname: Remor
authors.forename: Christian
authors.initials: C
authors.lastname: Höfert
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Schelder
authors.forename: Miro
authors.initials: M
authors.lastname: Brajenovic
authors.forename: Heinz
authors.initials: H
authors.lastname: Ruffner
authors.forename: Alejandro
authors.initials: A
authors.lastname: Merino
authors.forename: Karin
authors.initials: K
authors.lastname: Klein
authors.forename: Manuela
authors.initials: M
authors.lastname: Hudak
authors.forename: David
authors.initials: D
authors.lastname: Dickson
authors.forename: Tatjana
authors.initials: T
authors.lastname: Rudi
authors.forename: Volker
authors.initials: V
authors.lastname: Gnau
authors.forename: Angela
authors.initials: A
authors.lastname: Bauch
authors.forename: Sonja
authors.initials: S
authors.lastname: Bastuck
authors.forename: Bettina
authors.initials: B
authors.lastname: Huhse
authors.forename: Christina
authors.initials: C
authors.lastname: Leutwein
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Heurtier
authors.forename: Richard R
authors.initials: RR
authors.lastname: Copley
authors.forename: Angela
authors.initials: A
authors.lastname: Edelmann
authors.forename: Erich
authors.initials: E
authors.lastname: Querfurth
authors.forename: Vladimir
authors.initials: V
authors.lastname: Rybin
authors.forename: Gerard
authors.initials: G
authors.lastname: Drewes
authors.forename: Manfred
authors.initials: M
authors.lastname: Raida
authors.forename: Tewis
authors.initials: T
authors.lastname: Bouwmeester
authors.forename: Peer
authors.initials: P
authors.lastname: Bork
authors.forename: Bertrand
authors.initials: B
authors.lastname: Seraphin
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kuster
authors.forename: Gitte
authors.initials: G
authors.lastname: Neubauer
authors.forename: Giulio
authors.initials: G
authors.lastname: Superti-Furga
mesh_terms: D002478:Cells, Cultured; D002846:Chromatography, Affinity; D018390:Gene Targeting; D006801:Humans; D046911:Macromolecular Substances; D020543:Proteome / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*; D012680:Sensitivity and Specificity; D013045:Species Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D046911:Macromolecular Substances; D020543:Proteome; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins