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

Nature. 2002 Jan 10;415(6868):141-7. doi: 10.1038/415141a.

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.

MeSH terms

  • Cells, Cultured
  • Chromatography, Affinity
  • Gene Targeting
  • Humans
  • Macromolecular Substances
  • Proteome / genetics
  • Proteome / physiology*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / isolation & purification
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / physiology*
  • Sensitivity and Specificity
  • Species Specificity
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Macromolecular Substances
  • Proteome
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins