The DNA Packaging Motor of Bacteriophage phi29

噬菌体phi29的DNA包装马达

• 批准号: 10317524
• 负责人: Paul James Jardine
• 金额: $ 53.52万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10317524
• 关键词: ATP Hydrolysis; ATP phosphohydrolase; Address; Adenoviruses; Adopted; Animals; Antiviral Agents; Antiviral Therapy; Bacillus subtilis; Bacteriophages; Binding; Biochemical; Biological; Biological Assay; Biological Models; Biophysics; Capsid; Capsid Proteins; Cell physiology; Chemicals; Communication; Complex; Computer Analysis; Coupled; Cryoelectron Microscopy; DNA; DNA Packaging; Development; Disease; Double Stranded DNA Virus; Eukaryotic Cell; Event; Generations; Genetic; Genome; Grant; Head; Health; Herpesviridae; Hydrolysis; In Vitro; Mechanics; Medical; Modeling; Molecular; Molecular Conformation; Molecular Motors; Motion; Motor; Movement; Nature; Nucleic Acids; Nucleotides; Organism; Phase; Process; Protein Conformation; Proteins; Resolution; Sampling; Structure; System; Testing; Viral Packaging; Work; base; biological systems; crystallinity; density; design; drug discovery; ds-DNA; exhaustion; flexibility; image processing; insight; macromolecule; molecular dynamics; molecular recognition; mutant; nucleoside triphosphatase; operation; particle; response; single molecule; success; translocase; viral DNA

Project Summary/Abstract The mechanism of DNA packaging for double-stranded DNA viruses will be studied in the Bacillus subtilis bacteriophage f29, the most efficient in vitro viral packaging system known. Using an integrated genetic, biochemical, computational and structural approach, we will characterize protein conformational change and movement in the transiently assembled packaging motor during DNA encapsidation. The mechanism of packaging in f29 will serve as a model for animal virus packaging in the analogous herpesvirus and adenovirus systems, and aid in the search for new antiviral therapies. Due to similarities between the f29 ATPase and other ring translocases, insights gained from the study of f29 packaging will also provide insight into the basic principles of macromolecular motor function in higher organisms. To interrogate the mechanism of DNA packaging we will: 1. determine the molecular basis for force generation of the packaging motor; 2. elucidate the mechanism of nucleotide cycling for a complex multimeric ATPase; and 3. describe the nature of intermolecular communication that coordinates the action of a biological nanomotor.

项目摘要/摘要 将在芽孢杆菌中研究双链DNA病毒的DNA包装机制 枯草噬菌体F29是已知的最有效的体外病毒包装系统。使用一个 综合遗传，生化，计算和结构方法，我们将表征蛋白质 DNA期间瞬时组装的包装电机的构象变化和运动 封装。 F29中包装的机制将作为动物病毒包装的模型 在类似的疱疹病毒和腺病毒系统中，并有助于寻找新的抗病毒 疗法。由于F29 ATPase和其他环易位酶之间的相似之处，获得了见解 从F29包装的研究中，还将深入了解大分子的基本原理 较高生物体的运动功能。为了询问DNA包装的机制，我们将：1。 确定包装电机力产生的分子基础； 2。阐明 复杂多聚体ATPase的核苷酸循环机理；和3。描述的本质 分子间交流，可以协调生物纳米运动的作用。