Functional analysis of conserved hypothetical proteins in prokaryotes

原核生物保守假设蛋白的功能分析

• 批准号: 12775233
• 负责人: Dr. Peter Uetz
• 金额: --
• 依托单位: The Institute for Genomic Research
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2005
• 资助国家: 德国
• 起止时间: 2004-12-31 至 2007-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/12775233?language=en
• 关键词: Functional; analysis; conserved; hypothetical; proteins

Currently more than 100 bacterial genomes have been completely sequenced but about one third of their genes have no known function. I suggest to address this problem by identifying all physical interactions among the -1,000 proteins of Treponema pattidum by systematic two-hybrid screens. Interactions of uncharacterized proteins will suggest possible functions for these proteins. Although T, pallidum encodes about 750 proteins which are conserved in other bacteria, I suggest to concentrate on -180 conserved hypothetical proteins. Our screen will not only provide first functional insights into these proteins but this functional information can be confidently transferred to homologous proteins in more tractable model species such as E.. coli, in which our predictions can be experimentally verified, e.g. by generating mutations. The genome of T. pallidum is four times smaller, than the genome of E.. coli.. Thus our project will be more than one order of magnitude smaller than a comparable project in E. coli because the number of experiments grows exponentially with the number of genes. Pilot screens in our. laboratory using several flagellar proteins have shown that the proposed strategy is (1) highly efficient and informative, (2) provides novel information on both characterized and uncharacterized proteins, (3) makes correct functional (experimentally verifiable) predictions, and (4) will devise technologies that can be applied to other genomes as well, including eukaryotic ones.

目前，已有100多个细菌基因组完成了测序，但其中约三分之一的基因功能未知。我建议通过系统的双杂交筛选来确定-1,000种密螺旋体蛋白之间的所有物理相互作用，以解决这个问题。未确定特征的蛋白质的相互作用将暗示这些蛋白质可能的功能。虽然梅毒T，编码了大约750个在其他细菌中保守的蛋白质，但我建议集中在-180个保守的假设蛋白质上。我们的筛选不仅将提供对这些蛋白质的第一次功能洞察，而且这些功能信息可以自信地转移到更容易处理的模式物种中的同源蛋白质，如E。在大肠杆菌中，我们的预测可以通过实验来验证，例如通过产生突变。梅毒螺旋体的基因组比梅毒螺旋体基因组小四倍。Coli..因此，我们的项目将比在大肠杆菌中的一个可比项目小一个数量级以上，因为实验的数量随着基因数量的增加而指数增长。我们的飞行员屏幕。使用几种鞭毛蛋白的实验室已经表明，所提出的策略是(1)高效和信息量大，(2)提供关于特征和未特征蛋白质的新信息，(3)做出正确的功能(实验可验证的)预测，以及(4)将设计出也可以应用于其他基因组的技术，包括真核生物的基因组。