Finding Protein Sequence Motifs--methods And Applications

寻找蛋白质序列基序——方法和应用

• 批准号: 7594460
• 负责人: Eugene V Koonin
• 金额: $ 31.78万
• 依托单位: NATIONAL LIBRARY OF MEDICINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7594460
• 关键词: 6-chloropenicillanic acid S-sulfoxide; Amino Acid Motifs; Amino Acid Sequence; Antitoxins; Bacterial Chromosomes; Bacteriophages; Blast Cell; Class; Classification; Computing Methodologies; DNA Repair; Databases; Elements; Eukaryota; Eukaryotic Cell; Evolution; Genes; Genome; Goals; Immunity; Methods; Pattern; Peptide Sequence Determination; Plasmids; Positioning Attribute; Prokaryotic Cells; Proteins; RNA Binding; RNA Interference; Research; Structure; System; Tertiary Protein Structure; Toxin; Validation; Work; base; genome sequencing; human BCAR1 protein; innovation; markov model; novel; protein structure; response

The rapid accumulation of genome sequences and protein structures during the last decade has been paralleled by major advances in sequence database search methods. The powerful Position-Specific Iterating BLAST (PSI-BLAST) method developed at the NCBI formed the basis of our work on protein motif analysis. In addition, Hidden Markov Models (HMM) and protein structure comparison methods were applied. During the last year, we made further progress in detailed analysis of the classification, evolution, and functions of several classes of proteins. In particular, we studied in detail the protein domains that are involved in prokaryotic toxin-antitoxin cassettes and in systems of defense against selfish elements. We proposed previously that the group of so-called Cas proteins comprise a novel DNA repair system. The association of the cas genes with CRISPR and, especially, the presence, in CRISPR units, of unique inserts homologous to phage and plasmid genes made to modify this hypothesis. It appears most likely that CASS is a prokaryotic system of defense against phages and plasmids that functions via the RNAi mechanism. The functioning of this system seems to involve integration of fragments of foreign genes into archaeal and bacterial chromosomes yielding heritable immunity to the respective agents. However, it appears that this inheritance is extremely unstable on the evolutionary scale such that the repertoires of unique psiRNAs are completely replaced even in closely related prokaryotes, presumably, in response to rapidly changing repertoires of dominant phages and plasmids. Our work on the cas system has stimulated exprimental research, and the proposed mechanism has already received partial experimental validation. We also used computational methods to identify a novel toxin-antitoxin system that is predicted to function via RNA binding or cleavage. In addition, we explored mechanisms of protein innovation in eukaryotes, in particular, the patterns of evolution of vairous classes of multidomain proteins.

在过去十年中，基因组序列和蛋白质结构的快速积累与序列数据库搜索方法的重大进展相似。在NCBI开发的强大位置特异性迭代BLAST（PSI-BLAST）方法构成了我们在蛋白质基序分析方面的基础。另外，采用了隐藏的马尔可夫模型（HMM）和蛋白质结构比较方法。在去年，我们在对几类蛋白质的分类，进化和功能的详细分析中取得了进一步的进步。特别是，我们详细研究了与核毒素 - 抗毒素盒和针对自私元素的防御系统有关的蛋白质结构域。我们以前提出，所谓的CAS蛋白组包括一种新型的DNA修复系统。 CAS基因与CRISPR的关联，尤其是在CRISPR单元中的存在，独特的插入与噬菌体和质粒基因同源的插入以修改该假设。 Cass似乎很可能是一种针对通过RNAi机制起作用的噬菌体和质粒的防御性防御系统。该系统的功能似乎涉及将外国基因片段整合到古细菌和细菌染色体中，从而对各个药物产生可遗传的免疫力。但是，似乎在进化量表上，这种遗传非常不稳定，因此即使在密切相关的原核生物中，独特的psirnas的曲目也被完全替换，这大概是响应于迅速变化的主导噬菌体和质粒的快速变化的曲目。我们在CAS系统上的工作激发了征收研究，并且提出的机制已经得到了部分实验验证。我们还使用计算方法来识别一种新型的毒素 - 抗毒素系统，该系统预测通过RNA结合或裂解功能。此外，我们探索了真核生物中蛋白质创新的机制，特别是多域蛋白质的进化模式。