Structure and Function of Essential Nucleoprotein ComplexesAlong a Viral Genome Packaging Pathway

病毒基因组包装途径中必需核蛋白复合物的结构和功能

基本信息

  • 批准号:
    9920164
  • 负责人:
  • 金额:
    $ 37万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-05-01 至 2022-04-30
  • 项目状态:
    已结题

项目摘要

Project Summary. Bacteriophages play a major role in bacterial evolution, in mediating bacterial pathogenicity and antibiotic resistance, in modulating the human microbiome and they have great potential as nanotherapeutics. Understanding these issues with respect to human disease and harnessing their potential as theranostic agents requires a fundamental understanding of virus development. The genome packaging pathways are strongly conserved in the large double-stranded DNA (dsDNA) viruses, both prokaryotic and eukaryotic. In this broad class of viruses, a terminase enzyme is responsible for (i) excision of an individual genome from concatemeric substrate (genome maturation) and (ii) translocation of DNA into a procapsid shell (genome packaging). These functions are catalyzed by terminase enzymes assembled into discrete maturation and packaging motor complexes. Terminases are composed of a catalytic subunit and a DNA recognition subunit, both of which are essential for genome packaging in vivo. Structural and single-molecule studies have provided insight into packaging motor complexes composed of the catalytic subunit in isolation; however, there is little information on motor complexes containing both essential subunits. Further, there is a dearth of structural information on the equally essential maturation complex precursor. This is due, in part, to the absence of well-characterized holoenzyme preparations and a dearth of in vitro assays to comprehensively assess the pathway. We have developed rigorous assays in which the biochemical, biophysical and structural features of the lambda genome-packaging pathway can be defined in great detail. Using these tools, we propose to characterize the structural (cryo-electron microscopy) and functional (biophysical, kinetic) features of the maturation complex, which show mechanistic similarity to the tetrameric type IIE/F restriction endonucleases. We directly address an emerging controversy relating to the DNA architecture in the maturation complex that mediates complex stability. We next test the hypothesis that the lambda motor also functions as a tetrameric complex and that ATP hydrolysis by the motor is strongly cooperative; these features represent a significant departure from currently accepted paradigms. Finally, we characterize a putative "nucleotide switch" mechanism that controls the transition from the stable maturation complex to the dynamic motor complex bound to the capsid and we rigorously define the energy budget of the translocating motor. The proposed studies will provide structural and mechanistic detail on two sequential packaging complexes and their transition through the genome-packaging pathway. These features are shared by all of the dsDNA viruses that package genomes from concatemeric precursors (phage, herpes) and the results will be of broad and general significance.
项目总结。

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)

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Carlos Enrique Catalano其他文献

Letter to the Editor: Assignment of the 1H, 13C, and 15N resonances of the DNA binding domain of gpNu1, a genome packaging protein from bacteriophage λ
  • DOI:
    10.1023/a:1008306326438
  • 发表时间:
    2000-09-01
  • 期刊:
  • 影响因子:
    1.900
  • 作者:
    Tonny de Beer;Marcos Ortega;Nancy Berton;Qin Yang;Michael Overduin;Carlos Enrique Catalano
  • 通讯作者:
    Carlos Enrique Catalano

Carlos Enrique Catalano的其他文献

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{{ truncateString('Carlos Enrique Catalano', 18)}}的其他基金

Structure and Function of Essential Nucleoprotein Complexes Along a Viral Genome Packaging Pathway
病毒基因组包装途径中必需核蛋白复合物的结构和功能
  • 批准号:
    10660775
  • 财政年份:
    2018
  • 资助金额:
    $ 37万
  • 项目类别:
Mechanisms of Viral DNA Packaging: Biophysical, Biochemical, & Genetic Analysis
病毒 DNA 包装机制:生物物理、生物化学、
  • 批准号:
    8663379
  • 财政年份:
    2011
  • 资助金额:
    $ 37万
  • 项目类别:
Mechanisms of Viral DNA Packaging: Biophysical, Biochemical, & Genetic Analysis
病毒 DNA 包装机制:生物物理、生物化学、
  • 批准号:
    8460115
  • 财政年份:
    2011
  • 资助金额:
    $ 37万
  • 项目类别:
Mechanisms of Viral DNA Packaging: Biophysical, Biochemical, & Genetic Analysis
病毒 DNA 包装机制:生物物理、生物化学、
  • 批准号:
    8653579
  • 财政年份:
    2011
  • 资助金额:
    $ 37万
  • 项目类别:
Mechanisms of Viral DNA Packaging: Biophysical, Biochemical, & Genetic Analysis
病毒 DNA 包装机制:生物物理、生物化学、
  • 批准号:
    8260552
  • 财政年份:
    2011
  • 资助金额:
    $ 37万
  • 项目类别:
Mechanisms of Viral DNA Packaging: Biophysical, Biochemical, & Genetic Analysis
病毒 DNA 包装机制:生物物理、生物化学、
  • 批准号:
    8109182
  • 财政年份:
    2011
  • 资助金额:
    $ 37万
  • 项目类别:
Biochemical and Biophysical Characterization of HIV Env Trimer Spikes using Nanod
使用 Nanod 对 HIV 包膜三聚体尖峰进行生化和生物物理表征
  • 批准号:
    7929402
  • 财政年份:
    2010
  • 资助金额:
    $ 37万
  • 项目类别:
Biochemical and Biophysical Characterization of HIV Env Trimer Spikes using Nanod
使用 Nanod 对 HIV 包膜三聚体尖峰进行生化和生物物理表征
  • 批准号:
    8132448
  • 财政年份:
    2010
  • 资助金额:
    $ 37万
  • 项目类别:
Mechanistic Studies on a DNA Packaging Machine
DNA包装机的机理研究
  • 批准号:
    6655087
  • 财政年份:
    2001
  • 资助金额:
    $ 37万
  • 项目类别:
Mechanistic Studies on a Viral DNA Packaging Machine
病毒DNA包装机的机理研究
  • 批准号:
    7060385
  • 财政年份:
    2001
  • 资助金额:
    $ 37万
  • 项目类别:
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