Structural biology of DNA-packaging machines from dsDNA viruses

双链 DNA 病毒 DNA 包装机的结构生物学

• 批准号: 2733226
• 金额: --
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2733226
• 关键词: Structural; biology; DNA; packaging; machines

Viruses are the most common biological entities on our planet, infecting all living things. In humans, viral infections like herpes and poliovirus cause serious illnesses but, because they are impossible to eradicate using current treatments, they can also persist indefinitely. This persistence often leads to serious health complications, including cancer.Viruses can only replicate inside host cells. During infection, the virus uses specialized molecular machines to copy its genes and to load them into protective capsules, which then spread to other cells. This project will employ cryo-Electron Microscopy and X-ray crystallography to image the machines and watch them in action.Specific Aims:1) Produce virus particles or stable molecular assemblies of individual proteins and nucleic acids2) Determine structures by either X-ray crystallography or cryo-electron microscopy3) Analyse structures and probe biological mechanisms by site-directed mutagenesisNovelty:Understanding how large protein-nucleic acid machines function requires structural knowledge about individual components and complete macromolecular assemblies. Recent advances in cryo-EM approaches allow high resolution structural information to be obtained for complete, multiple component nucleic acid machines. Such structures could be complemented by X-ray structures of individual protein components determined at higher resolution. The project will target molecular motors, for which no structural information is currently available.

病毒是我们星球上最常见的生物实体，感染所有生物。在人类中，像疱疹和脊髓灰质炎病毒这样的病毒感染会导致严重的疾病，但是，因为它们不可能用目前的治疗方法根除，所以它们也可以无限期地持续下去。这种持续存在往往会导致严重的健康并发症，包括癌症。病毒只能在宿主细胞内复制。在感染过程中，病毒使用专门的分子机器复制其基因，并将其装入保护性胶囊中，然后扩散到其他细胞。本计画将利用冷冻电子显微镜和X光晶体学来观察这些机器的运作。具体目标：1）制造病毒粒子或个别蛋白质和核酸的稳定分子组合体2）利用X光晶体学或冷冻电子显微镜来确定结构3）利用定点突变来分析结构和探测生物机制新颖性：了解大型蛋白质-核酸机器如何运作，需要个别组分和完整大分子组合体的结构知识。冷冻EM方法的最新进展允许获得完整的多组分核酸机器的高分辨率结构信息。这种结构可以通过以更高分辨率确定的单个蛋白质组分的X射线结构来补充。该项目将针对分子马达，目前还没有结构信息。