Functional organization of the yeast proteome by systematic analysis of protein complexes.
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.
Gavin
Anne-Claude
AC
Cellzome AG, Meyerhofstrasse 1, 69117 Heidelberg, Germany. anne-claude.gavin@cellzome.com
Bösche
Markus
M
Krause
Roland
R
Grandi
Paola
P
Marzioch
Martina
M
Bauer
Andreas
A
Schultz
Jörg
J
Rick
Jens M
JM
Michon
Anne-Marie
AM
Cruciat
Cristina-Maria
CM
Remor
Marita
M
Höfert
Christian
C
Schelder
Malgorzata
M
Brajenovic
Miro
M
Ruffner
Heinz
H
Merino
Alejandro
A
Klein
Karin
K
Hudak
Manuela
M
Dickson
David
D
Rudi
Tatjana
T
Gnau
Volker
V
Bauch
Angela
A
Bastuck
Sonja
S
Huhse
Bettina
B
Leutwein
Christina
C
Heurtier
Marie-Anne
MA
Copley
Richard R
RR
Edelmann
Angela
A
Querfurth
Erich
E
Rybin
Vladimir
V
Drewes
Gerard
G
Raida
Manfred
M
Bouwmeester
Tewis
T
Bork
Peer
P
Seraphin
Bertrand
B
Kuster
Bernhard
B
Neubauer
Gitte
G
Superti-Furga
Giulio
G
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
D046911:Macromolecular Substances; D020543:Proteome; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins