Finding Protein Sequence Motifs--methods And Applications

寻找蛋白质序列基序——方法和应用

• 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
• 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/7735068
• 关键词: Amino Acid Motifs; Amino Acid Sequence; Antitoxins; Archaea; Bacteria; Bacteriophages; Blast Cell; Class; Classification; Complex; Computing Methodologies; DNA Repair; Databases; Eukaryota; Eukaryotic Cell; Evolution; Genome; Goals; Individual; Methods; Oxidoreductase; Pattern; Peptide Sequence Determination; Positioning Attribute; Proteins; Proteome; RNA Binding; RNA Interference; RNA Processing; Signal Transduction; Structure; System; Tertiary Protein Structure; Time; Toxin; Vesicle; Work; base; genome sequencing; innovation; intracellular protein transport; markov model; novel; protein structure; protein transport

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.

基因组序列和蛋白质结构在过去十年中的快速积累已经被序列数据库搜索方法的重大进展所证实。NCBI开发的强大的位置特异性迭代BLAST（PSI-BLAST）方法构成了我们蛋白质基序分析工作的基础。此外，隐马尔可夫模型（HMM）和蛋白质结构的比较方法。在过去的一年中，我们在详细分析几类蛋白质的分类，进化和功能方面取得了进一步的进展。具体来说，我们详细研究了参与真核RNA干扰机制的蛋白质结构域，并表明真核RNA干扰的蛋白质机制是从参与DNA修复和RNA加工的祖先古细菌、细菌和噬菌体蛋白质拼凑而成的。我们还使用计算方法来鉴定一种新的毒素-抗毒素系统，该系统被预测通过RNA结合或切割以及其他不同的机制发挥作用。我们探索了真核生物中蛋白质创新的一般机制，特别是各种多结构域蛋白质的进化模式，并表明有限的混杂结构域对真核生物蛋白质组和信号网络的多样性和可进化性做出了重大贡献。我们研究了几个可能对真核细胞起源很重要的单个结构域的分布和进化。特别地，已经表明存在于细菌和古细菌中的4-乙烯基还原酶（V4 R）蛋白结构域与TRAPP 1囊泡-束缚复合物的Bet 3亚基同源，该蛋白在所有真核生物中是保守的。这表明，第一次，一个关键的真核运输蛋白的原核起源。

项目成果

SPOUT: a class of methyltransferases that includes spoU and trmD RNA methylase superfamilies, and novel superfamilies of predicted prokaryotic RNA methylases.

• 发表时间: 2002
• 期刊: Journal of molecular microbiology and biotechnology
• 影响因子: 1.2
• 作者: Vivek Anantharaman;E. Koonin;L. Aravind

A novel family of P-loop NTPases with an unusual phyletic distribution and transmembrane segments inserted within the NTPase domain.

• DOI: 10.1186/gb-2004-5-5-r30
• 发表时间: 2004
• 期刊: Genome biology
• 影响因子: 12.3
• 作者: Aravind L;Iyer LM;Leipe DD;Koonin EV
• 通讯作者: Koonin EV

Origin and evolution of the archaeo-eukaryotic primase superfamily and related palm-domain proteins: structural insights and new members.

考古 - 核核原始酶超家族和相关棕榈域蛋白的起源和进化：结构见解和新成员。

• DOI: 10.1093/nar/gki702
• 发表时间: 2005
• 期刊: NUCLEIC ACIDS RESEARCH
• 影响因子: 14.9
• 作者: Iyer, LM;Koonin, EV;Leipe, DD;Aravind, L
• 通讯作者: Aravind, L

Extensive domain shuffling in transcription regulators of DNA viruses and implications for the origin of fungal APSES transcription factors.

• DOI: 10.1186/gb-2002-3-3-research0012
• 发表时间: 2002
• 期刊: Genome biology
• 影响因子: 12.3
• 作者: Iyer LM;Koonin EV;Aravind L
• 通讯作者: Aravind L

The rhomboids: a nearly ubiquitous family of intramembrane serine proteases that probably evolved by multiple ancient horizontal gene transfers.

• DOI: 10.1186/gb-2003-4-3-r19
• 发表时间: 2003
• 期刊: GENOME BIOLOGY
• 影响因子: 12.3
• 作者: Koonin, Eugene V;Makarova, Kira S;Rogozin, Igor B;Davidovic, Laetitia;Letellier, Marie-Claude;Pellegrini, Luca
• 通讯作者: Pellegrini, Luca