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 a de 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.

1. Cellzome AG, Meyerhofstrasse 1, 69117 Heidelberg, Germany
2. EMBL, Meyerhofstrasse 1, 69117 Heidelberg, Germany
3. MPI-MG, MPI-IB, Charité Campus Mitte, Schumannstrasse 21/22, 10117 Berlin, Germany
4. Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 19, 1090 Vienna, Austria
5. †Present address: EMBL, Meyerhofstrasse 1, 69117 Heidelberg, Germany
6. *These authors contributed equally to this work

Correspondence to: Robert B. Russell²Giulio Superti-Furga^1,4 Correspondence and requests for materials should be addressed to G.S.-F. (Email: gsuperti@cemm.oeaw.ac.at), R.B.R. (Email: russell@embl-heidelberg.de). Purification and complex data have been deposited at the IntAct database with accession numbers EBI-768904 (purifications) and EBI-765905 (author inferred complexes). The data, including the MS protein identifications, are accessible at http://yeast-complexes.embl.de, and the yeast strains are available from Euroscarf.

Received 17 October 2005 | Accepted 15 December 2005 |

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