《自然》(Nature 415: 6868 10 January 2002)杂志发表了来自两个小组的关于酵母Saccharomyces cerevisiae的大规模功能蛋白学研究结果。第一个小组所进行的是Cellzome、EMBL和CGM-CNRS三个机构之间的一项合作研究,共有超过1700个蛋白通过同源重组得以标记,其中1143个与人体生物学有关。对基因产物的质谱研究识别出了232个多蛋白复合物,还识别出344种蛋白的新的细胞功能。另一个小组的成员包括来自MDS Proteomics及三个加拿大研究机构的科学家,他们分析了所预测出的作为诱饵的酵母蛋白中的10%以上,检测出占该基因组25%的3617种相关蛋白。
Functional organization of the yeast proteome by systematic analysis
of protein complexes
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.