A comprehensive two-hybrid analysis to explore the yeast protein interactome

A comprehensive two-hybrid analysis to explore the yeast protein interactome
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DOI:
10.1073/pnas.061034498
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发表时间:
2001-04-10
影响因子:
11.1
通讯作者:
Sakaki, Y
Sakaki, Y
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Ito, T;Chiba, T;Sakaki, Y

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蛋白质之间的相互作用在各种生物功能的执行中起着至关重要的作用。因此,它们的全面描述将对全测序基因组的功能解释做出相当大的贡献,基因组中充斥着不可预测功能的新基因。我们之前开发了一个系统来检测发芽酵母的大约6000种蛋白质之间所有可能的组合中的双杂交相互作用。在这里,我们已经使用该系统完成了对3,278个蛋白质之间4549个双杂交相互作用的综合分析。出乎意料的是,这些数据与另一个项目获得的数据没有太大重叠[Uetz,P,等人。(2000)自然(伦敦)403,623-627],因此大大扩展了我们对酵母的蛋白质相互作用空间或相互作用组的知识。这些二元相互作用的累积连接产生了一个连接绝大多数蛋白质的单一的巨大网络。生物信息学辅助选择生物相关的相互作用突出了各种耐人寻味的子网络。例如,它们包括成功地预见到一种新的蛋白质参与纺锤体极体功能的研究,以及可能发现一种迄今未知的可能参与囊泡运输过程的多蛋白复合体的研究。因此,我们的数据将显著扩展和改进蛋白质相互作用图,以探索基因组功能,最终导致对细胞作为一个分子系统的彻底理解。
Protein-protein interactions play crucial roles in the execution of various biological functions. Accordingly, their comprehensive description would contribute considerably to the functional interpretation of fully sequenced genomes, which are flooded with novel genes of unpredictable functions. We previously developed a system to examine two-hybrid interactions in all possible combinations between the approximate to6,000 proteins of the budding yeast Saccharomyces cerevisiae. Here we have completed the comprehensive analysis using this system to identify 4,549 two-hybrid interactions among 3,278 proteins. Unexpectedly, these data do not largely overlap with those obtained by the other project [Uetz, P,, et al. (2000) Nature (London) 403, 623-627] and hence have substantially expanded our knowledge on the protein interaction space or interactome of the yeast. Cumulative connection of these binary interactions generates a single huge network linking the vast majority of the proteins. Bioinformatics-aided selection of biologically relevant interactions highlights various intriguing subnetworks. They include, for instance, the one that had successfully foreseen the involvement of a novel protein in spindle pole body function as well as the one that may uncover a hitherto unidentified multiprotein complex potentially participating in the process of vesicular transport. Our data would thus significantly expand and improve the protein interaction map for the exploration of genome functions that eventually leads to thorough understanding of the cell as a molecular system.