Finding Protein Sequence Motifs--methods And Applications

寻找蛋白质序列基序——方法和应用

基本信息

批准号：
7735068
负责人：
Eugene V Koonin
金额：
$ 32.76万
依托单位：
NATIONAL LIBRARY OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

项目摘要

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. Specifically, we studied in detail the protein domains that are involved in eukaryotic RNA interference mechanisms and showed that the protein machinery of eukaryotic RNAi was pieced together from ancestral archaeal, bacterial and phage proteins that are involved in DNA repair and RNA processing. We also used computational methods to identify a novel toxin-antitoxin systems that are predicted to function via RNA binding or cleavage and other, diverse mechanisms. We explored the general mechanisms of protein innovation in eukaryotes, in particular, the patterns of evolution of vairous classes of multidomain proteins and showed that a limited repertoire of promiscuous domains makes a major contribution to the diversity and evolvability of eukaryotic proteomes and signaling networks. We investigated the distribution and evolution of several individual domains that might have been important for the origin of eukaryotic cells. In particular, it has been shown that the 4-vinyl reductase (V4R) protein domain present in bacteria and archaea is homologous to the Bet3 subunit of the TRAPP1 vesicle-tethering complex that is conserved in all eukaryotes. This suggests, for the first time, a prokaryotic origin for one of the key eukaryotic trafficking 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。具体而言，我们详细研究了与真核RNA干扰机制有关的蛋白质结构域，并表明真核RNAi的蛋白质机械是从祖先古细菌，细菌和噬菌体蛋白中拼合在一起的，这些蛋白质与DNA修复和RNA处理有关。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结合或裂解以及其他不同机制起作用。我们探讨了真核生物中蛋白质创新的一般机制，特别是多域蛋白质的演变模式，并表明，滥交结构域的有限曲目对真核生物蛋白质组织和信号网络的多样性和可发展性的主要贡献。我们研究了几个单个领域的分布和演变，这可能对真核细胞的起源很重要。特别是，已经表明，细菌和古细菌中存在的4-乙烯基还原酶（V4R）蛋白结构域与在所有真核生物中保守的Trapp1囊泡螺旋菌合体的Bet3亚基同源。这首先提出了一种主要的真核运输蛋白之一的原核起源。