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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.

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Figure 1: Synopsis of the screen.
Figure 2: Statistics of proteins and complexes.
Figure 3: Primary validation of complex composition by ‘reverse’ purification: the polyadenylation machinery.
Figure 4: The protein complex network, and grouping of connected complexes.
Figure 5: Protein complexes have a similar composition in yeast and human.

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Acknowledgements

We thank C. Cohen, S. Artavanis-Tsakonas and F. Kafatos for suggestions and support throughout the work; C. Gässler, C. Kalla, N. Umhey and P. Völkel for help with experiments; K. Herzog and her team for media supply; E. Hurt and H. T. Timmers for sharing unpublished results and for suggestions; and numerous people at the European Molecular Biology Laboratory for help, especially G. Bricard, F. Caspary, O. Puig, G. Stier and members of the Nebreda, Superti-Furga, Klein, Wilm and Bork laboratories.

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Correspondence to Anne-Claude Gavin or Giulio Superti-Furga.

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Gavin, AC., Bösche, M., Krause, R. et al. Functional organization of the yeast proteome by systematic analysis of protein complexes. Nature 415, 141–147 (2002). https://doi.org/10.1038/415141a

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