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Proteome survey reveals modularity of the yeast cell machinery

Naturevolume 440, pages631–636 (2006)Cite this article

Abstract

Protein complexes are key molecular entities that integrate multiple gene products to perform cellular functions. Here we report the first genome-wide screen for complexes in an organism, budding yeast, using affinity purification and mass spectrometry. Through systematic tagging of open reading frames (ORFs), the majority of complexes were purified several times, suggesting screen saturation. The richness of the data set enabled ade novo characterization of the composition and organization of the cellular machinery. The ensemble of cellular proteins partitions into 491 complexes, of which 257 are novel, that differentially combine with additional attachment proteins or protein modules to enable a diversification of potential functions. Support for this modular organization of the proteome comes from integration with available data on expression, localization, function, evolutionary conservation, protein structure and binary interactions. This study provides the largest collection of physically determined eukaryotic cellular machines so far and a platform for biological data integration and modelling.

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Figure 1:Synopsis of the genome-wide screen for complexes and data analysis.
Figure 2:Evidence supporting complex organization.
Figure 3:Architecture and modularity of complexes.
Figure 4:Modularity of the yeast cellular machinery.
Figure 5:Phenotypic data mapped to complexes.

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Acknowledgements

We thank C. Cohen, S. Artavanis-Tsakonas, B. Seraphin and L. Serrano for support and suggestions throughout the work, and F. Weisbrodt for assistance with the graphics.

Author information

Author notes

  1. Anne-Claude Gavin

    Present address: EMBL, Meyerhofstrasse 1, 69117, Heidelberg, Germany

  2. Anne-Claude Gavin and Patrick Aloy: *These authors contributed equally to this work

Authors and Affiliations

  1. Cellzome AG, Meyerhofstrasse 1, 69117, Heidelberg, Germany

    Anne-Claude Gavin, Paola Grandi, Roland Krause, Markus Boesche, Martina Marzioch, Christina Rau, Sonja Bastuck, Birgit Dümpelfeld, Angela Edelmann, Marie-Anne Heurtier, Verena Hoffman, Christian Hoefert, Karin Klein, Manuela Hudak, Anne-Marie Michon, Malgorzata Schelder, Markus Schirle, Marita Remor, Tatjana Rudi, Andreas Bauer, Tewis Bouwmeester, Georg Casari, Gerard Drewes, Gitte Neubauer, Jens M. Rick, Bernhard Kuster & Giulio Superti-Furga

  2. EMBL, Meyerhofstrasse 1, 69117, Heidelberg, Germany

    Patrick Aloy, Lars Juhl Jensen, Sean Hooper, Peer Bork & Robert B. Russell

  3. MPI-MG, MPI-IB, Charité Campus Mitte, Schumannstrasse 21/22, 10117, Berlin, Germany

    Roland Krause

  4. Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 19, 1090, Vienna, Austria

    Giulio Superti-Furga

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Corresponding authors

Correspondence toRobert B. Russell orGiulio Superti-Furga.

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Competing interests

Purification and complex data have been deposited at the IntAct database (http://www.ebi.ac.uk/intact/) with accession numbers EBI-768904 (purifications) and EBI-765905 (author inferred complexes). The data, including the MS protein identifications, are accessible athttp://yeast-complexes.embl.de, and the yeast strains are available from Euroscarf (http://web.uni-frankfurt.de/fb15/mikro/euroscarf/col_index.html). Reprints and permissions information is available atnpg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

Supplementary information

Supplementary Notes

This file contains Supplementary Data and Supplementary Methods, including a detailed description of the screen for protein complexes with Supplementary Data on the proteome coverage. There is also a detailed description of the biochemical, mass spectrometry and bioinformatics methods. This file also contains Supplementary Figures 1–9 as supports to the points described above. (PDF 1196 kb)

Supplementary Table 1

List of all purifications and proteins retrieved. (PDF 344 kb)

Supplementary Table 2

List of all protein complexes. (PDF 202 kb)

Supplementary Table 3

List of all protein modules. (PDF 64 kb)

Supplementary Table 4

List of protein complexes purified only once and producing a signal too weak to be automatically deduced. (PDF 62 kb)

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Gavin, AC., Aloy, P., Grandi, P.et al. Proteome survey reveals modularity of the yeast cell machinery.Nature440, 631–636 (2006). https://doi.org/10.1038/nature04532

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Editorial Summary

A proteomics landmark

Two groups have completed extensive surveys of the protein–protein interactions of the yeastSaccharomyces cerevisiae. Gavinet al. identify 491 distinct protein complexes that act with other protein modules to make up yeast's cellular machinery. This work has also generated more than 5,000 new yeast strains for future analysis. And Kroganet al. identify 547 complexes, with an average of 4.9 proteins involved in each. Many yeast proteins are conserved in evolution, so these two important surveys are also relevant to many areas of human biology.

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