Organização funcional do proteoma de levedura através da análise sistemática dos complexos de proteínas

Nature 415, 141-147 (10 January 2002) | doi:10.1038/415141a; Received 15 August 2001; Accepted 25 October 2001

Functional organization of the yeast proteome by systematic analysis of protein complexes

Anne-Claude Gavin¹, Markus Bösche¹, Roland Krause¹, Paola Grandi¹, Martina Marzioch¹, Andreas Bauer¹, Jörg Schultz¹, Jens M. Rick¹, Anne-Marie Michon¹, Cristina-Maria Cruciat¹, Marita Remor¹, Christian Höfert¹, Malgorzata Schelder¹, Miro Brajenovic¹, Heinz Ruffner¹, Alejandro Merino¹, Karin Klein¹, Manuela Hudak¹, David Dickson¹, Tatjana Rudi¹, Volker Gnau¹, Angela Bauch¹, Sonja Bastuck¹, Bettina Huhse¹, Christina Leutwein¹, Marie-Anne Heurtier¹, Richard R. Copley², Angela Edelmann¹, Erich Querfurth¹, Vladimir Rybin¹, Gerard Drewes¹, Manfred Raida¹, Tewis Bouwmeester¹, Peer Bork², Bertrand Seraphin^2,3, Bernhard Kuster¹, Gitte Neubauer¹ & Giulio Superti-Furga^1,2

1. Cellzome AG, Meyerhofstrasse 1, 69117 Heidelberg, Germany
2. European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
3. CGM-CNRS, 91198 Gif sur Yvette Cedex, France

Correspondence to: Anne-Claude Gavin¹Giulio Superti-Furga^1,2 Correspondence and requests for materials should be addressed to A.C.G. (e-mail: Email: anne-claude.gavin@cellzome.com) or G.S.F. (Email: giulio.superti-furga@cellzome.com). The data are accessible athttp://yeast.cellzome.com.

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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Darwin era totalmente ignorante de tudo isso acima.

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