Functional organization of the yeast proteome by systematic analysis of protein complexes
Functional organization of the yeast proteome by systematic analysis of protein complexes
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DOI：
10.1038/415141a
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发表时间：
2002-01-10
期刊：
影响因子：
64.8
通讯作者：
Superti-Furga, G
中科院分区：
文献类型：
--
作者：
Gavin, AC;Bösche, M;Superti-Furga, G
大多数细胞过程是通过多蛋白复合物进行的。对其组件的识别和分析提供了有关如何将表达蛋白质（蛋白质组）组合到功能单元中的洞察力。我们在大规模方法中使用了串联亲属纯化（TAP）和质谱法来表征酿酒酵母中多蛋白络合物。我们处理了1,739个基因，其中包括与人类生物学相关的1,143个人直系同源物，并纯化了589个蛋白质组件。对这些组件的生物信息学分析定义了232个不同的多蛋白复合物，并提出了344种蛋白质的新细胞作用，其中包括231种蛋白质，没有以前的功能性注释。酵母和人类复合物的比较表明，跨物种的保护从单蛋白延伸到其分子环境。我们的分析提供了真核蛋白质组作为二进制相互作用以外组织水平的蛋白质复合物网络的轮廓。这张高阶地图包含基本的生物学信息，并为一种更有道理和知情的药物发现方法提供了背景。
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.