A Human Protein-Protein Interaction Network: A Resource for Annotating the Proteome

Summery：

Protein-protein interaction maps provide a valuable framework for a better understanding of the functional organization of the proteome. To detect interacting pairs of human proteins systematically, a protein matrix of 4456 baits and 5632 preys was screened by automated yeast two-hybrid (Y2H) interaction mating. We identified 3186 mostly novel interactions among 1705 proteins, resulting in a large, highly connected network. Independent pull-down and coimmunoprecipitation assays validated the overall quality of the Y2H interactions. Using topological and GO criteria, a scoring system was developed to define 911 high-confidence interactions among 401 proteins. Furthermore, the network was searched for interactions linking uncharacterized gene products and human disease proteins to regulatory cellular pathways. Two novel Axin-1 interactions were validated experimentally, characterizing ANP32A and CRMP1 as modulators of Wnt signaling. Systematic human protein interaction screens can lead to a more comprehensive understanding of protein function and cellular processes.
　

    蛋白蛋白相互作用为我们更好的理解蛋白组的组织功能提供了一个很好的基础。为了系统的检测人类蛋白的相互作用对，作者们设计了4456个bait和5632个prey用自动的酵母双杂交技术筛选相互之间的作用关系。作者检测到了1705个蛋白之间，3185个相互作用，这些相互作用大部分是新检测到的，并组成了一个很大的高联通的网络。为了检验酵母双杂交的可靠性，作者还随机抽取了部分相互作用用pull-down和coimmunoprecipitation实验进行了检验。同时，作者利用拓扑学和GO分类，构建了一个打分系统给得到的相互作用打分，得到了由401个蛋白组成的911个高可信度的相互作用关系。作者们进一步分析了这个网络里面未知功能的蛋白和跟疾病相关蛋白与细胞调控通路的关系，发现了两个新的Axin-1相互作用并被实验证实，及ANP32A and CRMP1在Wnt信号通路里的调控作用。相信这种系统的人类蛋白相互作用的筛选能够帮助人们进一步理解蛋白的功能和细胞进程。　

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