The Replication Initiator Protein E1 and its Interaction with DNA

复制起始蛋白 E1 及其与 DNA 的相互作用

• 批准号: 8084114
• 负责人: Leemor Joshua-Tor
• 金额: $ 30.45万
• 依托单位: COLD SPRING HARBOR LABORATORY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8084114
• 关键词: Antiviral Agents; Antiviral Therapy; Binding; Bovine Papillomavirus; Characteristics; Complex; Crystallization; DNA; DNA Binding Domain; DNA biosynthesis; DNA-Protein Interaction; Development; Event; Family; Goals; Growth; Human Papillomavirus; Human Virus; Investigation; L-Selenomethionine; Length; Link; Malignant Neoplasms; Membrane Proteins; Methods; Molecular; Molecular Conformation; Molecular Structure; Nucleotides; Oligonucleotides; Papillomavirus; Parents; Population; Production; Property; Protein Footprinting; Proteins; Relative (related person); Replication Initiation; Replication Origin; Resolution; Sampling; Shapes; Solubility; Solutions; Structure; System; Testing; Viral; Viral Proteins; Virus; Virus Diseases; Work; base; genital infection; helicase; improved; origin recognition complex; prototype; replication initiator protein; research study; vaccine development; viral DNA

DESCRIPTION (provided by applicant): Papillomaviruses are a large family of closely related viruses that give rise to warts in their hosts. Infection of the genital tract by the human viruses from this group represents one of the few firmly established links between viral infection and the development of cancer. The bovine papillomavirus, BPV, has served as a prototype for this group especially regarding viral DNA replication, but its relative simplicity serves also to examine mechanistic features of DNA replication in general. This system, whereby a single protein encompasses the key events in replication initiation through its different oligomeric forms, provides a great opportunity to examine these events in detail. Our goals are to build a mechanistic view of the assembly of E1 on the origin of replication and an understanding toward the workings of hexameric helicases in general at an atomic level. In addition, the viral DNA replication machinery itself represents an obvious target for antiviral therapy. Detailed information such as high-resolution structures of viral proteins required for replication will greatly facilitate the development and testing of antiviral agents. Relevance: infection of the genital tract by the human papillomaviruses represents one of the few firmly established links between viral infection and the development of cancer. The bovine papillomavirus, BPV, has served as a prototype for this group especially regarding viral replication. It also enables the understanding of key features in DNA replication in general due to its relative simplicity Our objective is to gain a mechanistic understanding of the events that initiate viral replication. This type of detailed information of viral proteins required for its replication and that can serve as targets for antiviral therapy, will greatly facilitate the development and testing of antiviral agents. Through there have been important recent advances in vaccine development, these may not be effective to a population that has already been infected.

描述（由申请方提供）：乳头瘤病毒是一个大家族的密切相关的病毒，可在其宿主中引起疣。人类生殖道被这组病毒感染代表了病毒感染与癌症发展之间为数不多的牢固联系之一。牛乳头状瘤病毒，BPV，已作为这组的原型，特别是关于病毒DNA复制，但其相对简单的也用于检查一般的DNA复制的机制特征。这个系统，其中一个单一的蛋白质包括复制起始的关键事件，通过其不同的寡聚体形式，提供了一个很好的机会，详细检查这些事件。我们的目标是建立一个机械视图的复制起点上的组装E1和六聚体解旋酶在原子水平上的工作一般的理解。此外，病毒DNA复制机制本身也是抗病毒治疗的一个明显靶点。复制所需的病毒蛋白质的高分辨率结构等详细信息将极大地促进抗病毒剂的开发和测试。相关性：人乳头瘤病毒对生殖道的感染是病毒感染与癌症发展之间少数牢固确立的联系之一。牛乳头状瘤病毒，BPV，已作为这一组的原型，特别是关于病毒复制。它也使一般的DNA复制的关键特征的理解，由于其相对简单，我们的目标是获得启动病毒复制的事件的机制的理解。这种病毒复制所需的病毒蛋白质的详细信息，可以作为抗病毒治疗的目标，将大大促进抗病毒药的开发和测试。尽管最近在疫苗开发方面取得了重要进展，但这些疫苗可能对已经感染的人群无效。