Evolutionary Analysis and Comparative Genomics of Protein Superfamilies
蛋白质超家族的进化分析和比较基因组学
基本信息
- 批准号:7735093
- 负责人:
- 金额:$ 22.42万
- 依托单位:
- 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
- 来源:
- 关键词:ATP phosphohydrolaseATPase DomainActive SitesAdenovirusesAnatomyAnimal ModelAnimalsArchitectureBacteriaBindingBiologicalBiological ProcessBiologyC-terminalCatalysisChromatinChromatin StructureChromosomesClassificationCodeComparative Genomic AnalysisComplexCysteineDNADNA Binding DomainDNA Modification ProcessDNA PackagingDNA VirusesDemographyDrosophila genusElementsEntamoeba histolyticaEnzymatic BiochemistryEnzymesEpigenetic ProcessEukaryotaEukaryotic CellEvolutionFamilyFutureGenesGenetic TranscriptionGenomicsGiardiaHelix-Turn-Helix MotifsHistidineHistone CodeHistonesIndividualInvestigationLifeLigaseLipidsLocationMechanicsMediatingMembraneMembrane LipidsMethyltransferaseMicroscopicModificationMolecularMotorNaegleriaNeighborhoodsNucleic AcidsNucleosomesNumbersOomycetesOrganismParasitesPathway interactionsPeptidesPhytophthoraPlayPortal SystemPositioning AttributePoxviridaeProtein AnalysisProtein BindingProtein IsoformsProteinsProteomePumpReactionRecording of previous eventsRelative (related person)ReportingResearch PersonnelRoleSWI2/SNF2ShapesSignal TransductionSisterStructureSurgical FlapsSystemTailTertiary Protein StructureTrichomonasTrichomonas vaginalisUbiquitinUbiquitin Like ProteinsViralViral PackagingViral ProteinsVirusbasechromatin proteinchromatin remodelingcomparativegenome sequencinghistone acetyltransferasehistone methyltransferaseinnovationmembernovelnucleaseprotein protein interactionreconstructionresearch studyscaffoldsizeterminasetranscription factortransposon/insertion elementviral DNA
项目摘要
1)Comparative Genomics and Evolutionary Trajectories of Viral ATP Dependent DNA-Packaging Systems.
We performed a comparative genomics study of ATP-dependent DNA packaging systems of viruses. Several distinct ATPase motors and accessory proteins have been identified in DNA-packaging systems of viruses such as terminase-portal systems, the phi29-like packaging apparatus, and packaging systems of lipid inner-membrane-containing viruses. Sequence and structure analysis of these proteins suggest that there were two major independent innovations of ATP-dependent DNA packaging systems in the viral universe. The first of these utilizes a HerA/FtsK superfamily ATPase and is seen in prokaryotic viruses with inner lipid membranes, large eukaryotic nucleo-cytoplasmic DNA viruses (including poxviruses) and a group of eukaryotic mobile DNA transposons. We showed that ATPases of the phi29-like packaging system are also divergent versions of the HerA/FtsK superfamily that functions in viruses without an inner membrane. The second system, the terminase-portal system, is dominant in prokaryotic tailed viruses and typically functions with linear chromosomes. The large subunit of this system contains a distinct ATPase domain and a C-terminal nuclease domain of the RNAse H fold. We developed the classification of these ATPases within the P-loop NTPases, genomic demography and positioning of their genes in the viral chromosome. We showed that diverse portal proteins utilized by these systems share a common evolutionary origin and might have frequently displaced each other in evolution. Examination of conserved gene neighborhoods indicates repeated acquisition of Helix-turn-Helix domaincontaining terminase small subunits and a third accessory component, the MuF protein. Adenoviruses appear to have evolved a third packaging ATPase, unique to their lineage. Relationship between one major type of packaging ATPases and cellular chromosome pumps like FtsK suggests an ancient common origin for viral packaging and cellular chromosome partitioning systems.
2)Comparative genomics of transcription factors and chromatin proteins in parasitic protists and other eukaryotes.
Comparative genomics of parasitic protists and their free-living relatives are profoundly impacting our understanding of the regulatory systems involved in transcription and chromatin dynamics. While some parts of these systems are highly conserved, other parts are rapidly evolving, thereby providing the molecular basis for the variety in the regulatory adaptations of eukaryotes. The gross number of specific transcription factors and chromatin proteins are positively correlated with proteome size in eukaryotes. However, the individual types of specific transcription factors show an enormous variety across different eukaryotic lineages. The dominant families of specific transcription factors even differ between sister lineages, and have been shaped by gene loss and lineage-specific expansions. Recognition of this principle has helped in identifying the hitherto unknown, major specific transcription factors of several parasites, such as apicomplexans, Entamoeba histolytica, Trichomonas vaginalis, Phytophthora and ciliates. Comparative analysis of predicted chromatin proteins from protists allows reconstruction of the early evolutionary history of histone and DNA modification, nucleosome assembly and chromatin-remodeling systems. Many key catalytic, peptide-binding and DNA-binding domains in these systems ultimately had bacterial precursors, but were put together into distinctive regulatory complexes that are unique to the eukaryotes. In the case of histone methylases, histone demethylases and SWI2/SNF2 ATPases, proliferation of paralogous families followed by acquisition of novel domain architectures, seem to have played a major role in producing a diverse set of enzymes that create and respond to an epigenetic code of modified histones. The diversification of histone acetylases and DNA methylases appears to have proceeded via repeated emergence of new versions, most probably via transfers from bacteria to different eukaryotic lineages, again resulting in lineage-specific diversity in epigenetic signals. Even though the key histone modifications are universal to eukaryotes, domain architectures of proteins binding post-translationally modified-histones vary considerably across eukaryotes. This indicates that the histone code might be "interpreted" differently from model organisms in parasitic protists and their relatives. The complexity of domain architectures of chromatin proteins appears to have increased during eukaryotic evolution. Thus, Trichomonas, Giardia, Naegleria and kinetoplastids have relatively simple domain architectures, whereas apicomplexans and oomycetes have more complex architectures. RNA-dependent post-transcriptional silencing systems, which interact with chromatin-level regulatory systems, show considerable variability across parasitic protists, with complete loss in many apicomplexans and partial loss in Trichomonas vaginalis. This evolutionary synthesis offers a robust scaffold for future investigation of transcription and chromatin structure in parasitic protists.
3)Anatomy of the E2 ligase fold: implications for enzymology and evolution of ubiquitin/Ub-like protein conjugation.
The configuration of the active site of E2 ligases, central enzymes in the ubiquitin/ubiquitin-like protein (Ub/Ubl) conjugation systems, has long puzzled researchers. Taking advantage of the wealth of newly available structures and sequences of E2s from diverse organisms, we performed a large-scale comparative analysis of these proteins. As a result we identified a previously under-appreciated diversity in the active site of these enzymes, in particular, the spatial location of the catalytic cysteine and a constellation of associated conserved residues that potentially contributes to catalysis. We observed structural innovations of differing magnitudes occurring in various families across the E2 fold that might correlate in part with differences in target interaction. A key finding was the independent emergence on multiple occasions of a polar residue, often a histidine, in the vicinity of the catalytic cysteine in different E2 families. We propose that these convergently emerging polar residues have a common function, such as in the stabilization of oxyanion holes during Ub/Ubl transfer and spatial localization of the Ub/Ubl tails in the active site. Thus, the E2 ligases represent a rare example in enzyme evolution of high structural diversity of the active site and position of the catalytic residue despite all characterized members catalyzing a similar reaction. Our studies also indicated certain evolutionarily conserved features in all active members of the E2 superfamily that stabilize the unusual flap-like structure in the fold. These features are likely to form a critical mechanical element of the fold required for catalysis. The results presented here could aid in new experiments to understand E2 catalysis.
BEN: a novel domain in chromatin factors and DNA viral proteins.
We reported a previously uncharacterized alpha-helical module, the BEN domain, in diverse animal proteins such as BANP/SMAR1, NAC1 and the Drosophila mod(mdg4) isoform C, in the chordopoxvirus virosomal protein E5R and in several proteins of polydnaviruses. Contextual analysis suggests that the BEN domain mediates protein-DNA and protein-protein interactions during chromatin organization and transcription. The presence of BEN domains in a poxviral early virosomal protein and in polydnaviral proteins also suggests a possible role for them in organization of viral DNA during replication or transcription.
1) 病毒 ATP 依赖性 DNA 包装系统的比较基因组学和进化轨迹。
我们对病毒的 ATP 依赖性 DNA 包装系统进行了比较基因组学研究。在病毒的 DNA 包装系统中,例如终止酶门系统、phi29 样包装装置和含脂质内膜病毒的包装系统中,已鉴定出几种不同的 ATP 酶马达和辅助蛋白。这些蛋白质的序列和结构分析表明,病毒宇宙中依赖 ATP 的 DNA 包装系统存在两次主要的独立创新。其中第一个利用 HerA/FtsK 超家族 ATP 酶,见于具有内脂膜的原核病毒、大型真核核细胞质 DNA 病毒(包括痘病毒)和一组真核移动 DNA 转座子。我们发现,phi29 样包装系统的 ATP 酶也是 HerA/FtsK 超家族的不同版本,该超家族在没有内膜的病毒中发挥作用。第二个系统,即终止酶门系统,在原核有尾病毒中占主导地位,通常与线性染色体一起发挥作用。该系统的大亚基包含一个独特的 ATP 酶结构域和一个 RNAse H 折叠的 C 端核酸酶结构域。我们开发了这些 ATP 酶在 P 环 NTP 酶内的分类、基因组人口统计学及其基因在病毒染色体中的定位。我们表明,这些系统利用的不同门户蛋白具有共同的进化起源,并且可能在进化中经常相互取代。对保守基因邻域的检查表明,重复获得了含有终止酶小亚基和第三个辅助成分 MuF 蛋白的螺旋-转角-螺旋结构域。腺病毒似乎进化出了第三种包装 ATP 酶,这是其谱系所独有的。一种主要类型的包装 ATP 酶与 FtsK 等细胞染色体泵之间的关系表明病毒包装和细胞染色体分配系统具有古老的共同起源。
2)寄生原生生物和其他真核生物转录因子和染色质蛋白的比较基因组学。
寄生原生生物及其自由生活亲属的比较基因组学正在深刻地影响我们对转录和染色质动力学调控系统的理解。虽然这些系统的某些部分高度保守,但其他部分正在快速进化,从而为真核生物调节适应的多样性提供了分子基础。真核生物中特定转录因子和染色质蛋白的总数与蛋白质组大小呈正相关。然而,特定转录因子的个体类型在不同的真核谱系中表现出巨大的多样性。特定转录因子的主要家族甚至在姐妹谱系之间也有所不同,并且是由基因丢失和谱系特异性扩展所塑造的。对这一原理的认识有助于识别几种寄生虫的迄今为止未知的主要特异性转录因子,例如顶端复门虫、溶组织内阿米巴、阴道毛滴虫、疫霉属和纤毛虫。对原生生物预测的染色质蛋白进行比较分析,可以重建组蛋白和 DNA 修饰、核小体组装和染色质重塑系统的早期进化历史。这些系统中的许多关键催化、肽结合和 DNA 结合结构域最终都有细菌前体,但被组合在一起形成真核生物特有的独特调节复合物。就组蛋白甲基化酶、组蛋白去甲基化酶和 SWI2/SNF2 ATP 酶而言,旁系同源家族的增殖以及随后获得新的结构域结构,似乎在产生多种酶的过程中发挥了重要作用,这些酶创建并响应修饰组蛋白的表观遗传密码。组蛋白乙酰化酶和 DNA 甲基化酶的多样化似乎是通过新版本的重复出现而进行的,最有可能是通过从细菌转移到不同的真核谱系,再次导致表观遗传信号的谱系特异性多样性。尽管关键的组蛋白修饰对于真核生物是通用的,但结合翻译后修饰组蛋白的蛋白质的结构域结构在真核生物之间存在很大差异。这表明组蛋白密码的“解释”可能与寄生原生生物及其近亲中的模式生物不同。染色质蛋白结构域的复杂性似乎在真核进化过程中有所增加。因此,毛滴虫、贾第鞭毛虫、耐格里虫和动质体具有相对简单的结构域,而顶端复合菌和卵菌则具有更复杂的结构。 RNA依赖性转录后沉默系统与染色质水平调节系统相互作用,在寄生原生生物中表现出相当大的变异性,许多顶端复合体完全丧失,阴道毛滴虫部分丧失。这种进化合成为未来研究寄生原生生物的转录和染色质结构提供了强大的支架。
3)E2连接酶折叠的解剖:对泛素/Ub样蛋白缀合的酶学和进化的影响。
E2 连接酶是泛素/泛素样蛋白 (Ub/Ubl) 缀合系统中的核心酶,其活性位点的配置长期以来一直困扰着研究人员。利用来自不同生物体的大量新可用的 E2 结构和序列,我们对这些蛋白质进行了大规模的比较分析。结果,我们发现了这些酶活性位点的先前未被充分认识的多样性,特别是催化半胱氨酸的空间位置和可能有助于催化的相关保守残基群。我们观察到 E2 折叠的各个家族中发生了不同程度的结构创新,这可能部分与目标相互作用的差异相关。一个关键发现是在不同 E2 家族的催化半胱氨酸附近多次独立出现极性残基(通常是组氨酸)。我们认为这些逐渐出现的极性残基具有共同的功能,例如在 Ub/Ubl 转移过程中稳定氧阴离子空穴以及活性位点中 Ub/Ubl 尾部的空间定位。因此,E2 连接酶代表了酶进化中活性位点和催化残基位置高度结构多样性的罕见例子,尽管所有特征成员都催化类似的反应。我们的研究还表明,E2 超家族的所有活跃成员都具有某些进化上保守的特征,这些特征稳定了折叠中不寻常的瓣状结构。这些特征可能形成催化所需的折叠的关键机械元件。这里提出的结果可以帮助新的实验来理解 E2 催化。
BEN:染色质因子和 DNA 病毒蛋白中的一个新结构域。
我们报道了一种先前未表征的α螺旋模块,即BEN结构域,存在于多种动物蛋白中,例如BANP/SMAR1、NAC1和果蝇mod(mdg4)亚型C、脊索痘病毒病毒体蛋白E5R和多DNA病毒的几种蛋白中。上下文分析表明,BEN 结构域在染色质组织和转录过程中介导蛋白质-DNA 和蛋白质-蛋白质相互作用。痘病毒早期病毒体蛋白和多DNA病毒蛋白中BEN结构域的存在也表明它们在复制或转录过程中病毒DNA的组织中可能发挥作用。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Aravind Iyer其他文献
Aravind Iyer的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Aravind Iyer', 18)}}的其他基金
Evolutionary Analysis and Comparative Genomics of Protein Superfamilies
蛋白质超家族的进化分析和比较基因组学
- 批准号:
9564629 - 财政年份:
- 资助金额:
$ 22.42万 - 项目类别:
Evolutionary Analysis and Comparative Genomics of Protein Superfamilies
蛋白质超家族的进化分析和比较基因组学
- 批准号:
8558127 - 财政年份:
- 资助金额:
$ 22.42万 - 项目类别:
Evolutionary Analysis and Comparative Genomics of Protein Superfamilies
蛋白质超家族的进化分析和比较基因组学
- 批准号:
8149617 - 财政年份:
- 资助金额:
$ 22.42万 - 项目类别:
Evolutionary Analysis and Comparative Genomics of Protein Superfamilies
蛋白质超家族的进化分析和比较基因组学
- 批准号:
8344972 - 财政年份:
- 资助金额:
$ 22.42万 - 项目类别:
Evolutionary Analysis and Comparative Genomics of Protein Superfamilies
蛋白质超家族的进化分析和比较基因组学
- 批准号:
10018682 - 财政年份:
- 资助金额:
$ 22.42万 - 项目类别:
Evolutionary Analysis and Comparative Genomics of Protein Superfamilies
蛋白质超家族的进化分析和比较基因组学
- 批准号:
7594479 - 财政年份:
- 资助金额:
$ 22.42万 - 项目类别:
Evolutionary Analysis and Comparative Genomics of Protein Superfamilies
蛋白质超家族的进化分析和比较基因组学
- 批准号:
10269689 - 财政年份:
- 资助金额:
$ 22.42万 - 项目类别:
Evolutionary Analysis and Comparative Genomics of Protein Superfamilies
蛋白质超家族的进化分析和比较基因组学
- 批准号:
8943249 - 财政年份:
- 资助金额:
$ 22.42万 - 项目类别:
Evolutionary Analysis and Comparative Genomics of Protein Superfamilies
蛋白质超家族的进化分析和比较基因组学
- 批准号:
7969254 - 财政年份:
- 资助金额:
$ 22.42万 - 项目类别:
相似海外基金
CRYSTAL STRUCTURE OF ADP COMPLEX OF ATPASE DOMAIN OF CHAPERONE HSC66
伴侣HSC66的ATP酶域ADP复合物的晶体结构
- 批准号:
6119556 - 财政年份:1999
- 资助金额:
$ 22.42万 - 项目类别: