Ito Takashi, Ota Kazuhisa, Kubota Hiroyuki, Yamaguchi Yoshihiro, Chiba Tomoko, Sakuraba Kazumi, Yoshida Mikio
Division of Genome Biology, Cancer Research Institute, Kanazawa University, Kanazawa 920-0934, Japan.
Mol Cell Proteomics. 2002 Aug;1(8):561-6. doi: 10.1074/mcp.r200005-mcp200.
Comprehensive analysis of protein-protein interactions is a challenging endeavor of functional proteomics and has been best explored in the budding yeast. The yeast protein interactome analysis was achieved first by using the yeast two-hybrid system in a proteome-wide scale and next by large-scale mass spectrometric analysis of affinity-purified protein complexes. While these interaction data have led to a number of novel findings and the emergence of a single huge network containing thousands of proteins, they suffer many false signals and fall short of grasping the entire interactome. Thus, continuous efforts are necessary in both bioinformatics and experimentation to fully exploit these data and to proceed another step forward to the goal. Computational tools to integrate existing biological knowledge buried in literature and various functional genomic data with the interactome data are required for biological interpretation of the huge protein interaction network. Novel experimental methods have to be developed to detect weak, transient interactions involving low abundance proteins as well as to obtain clues to the biological role for each interaction. Since the yeast two-hybrid system can be used for the mapping of the interaction domains and the isolation of interaction-defective mutants, it would serve as a technical basis for the latter purpose, thereby playing another important role in the next phase of protein interactome research.
蛋白质-蛋白质相互作用的全面分析是功能蛋白质组学中一项具有挑战性的工作，在芽殖酵母中得到了最好的探索。酵母蛋白质相互作用组分析首先通过在全蛋白质组规模上使用酵母双杂交系统实现，其次通过对亲和纯化的蛋白质复合物进行大规模质谱分析实现。虽然这些相互作用数据带来了许多新发现，并出现了一个包含数千种蛋白质的单一巨大网络，但它们存在许多错误信号，并且未能掌握整个相互作用组。因此，在生物信息学和实验方面都需要持续努力，以充分利用这些数据，并朝着目标再前进一步。为了对巨大的蛋白质相互作用网络进行生物学解释，需要计算工具来整合文献中隐藏的现有生物学知识以及各种功能基因组数据与相互作用组数据。必须开发新的实验方法来检测涉及低丰度蛋白质的弱的、瞬时相互作用，并获得每种相互作用的生物学作用线索。由于酵母双杂交系统可用于绘制相互作用结构域和分离相互作用缺陷突变体，它将作为实现后一目标的技术基础，从而在蛋白质相互作用组研究的下一阶段发挥另一个重要作用。
