Determining structure of the Pre-Initiation RNA-protein Complex formed during canonical translation initiation of HIV mRNA

确定 HIV mRNA 经典翻译起始过程中形成的起始前 RNA-蛋白质复合物的结构

• 批准号: 2448421
• 金额: --
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2448421
• 关键词: Determining; structure; Pre; Initiation; RNA

Viruses such as HIV are a leading cause of emerging infectious diseases and persistent pandemics. Being obligate parasites, they also depend heavily on the host cell machinery to propagate their own life cycle. Yet, surprisingly, we lack a comprehensive understanding of the structure and dynamics of the viral-human complexes that facilitate virus replication and disease progression in the cell. For example, less than 0.01% entries deposited in the Protein Data Bank till date pertain to RNA-protein (RNP) complexes formed from both human and virus components. Thus, in the proposed study, we will use an integrated structural biology approach involving a combination of experimental biochemistry and theoretical biophysics techniques (including X-ray crystallography, cryo-Electron Microscopy and Molecular Dynamics simulations) to investigate the role of the biochemically well characterised HIV TAR RNA element and Tat protein in translation initiation of HIV mRNA by determining high-resolution structure of the HIV-host Pre-Initiation Complex.

艾滋病毒等病毒是新出现的传染病和持续流行病的主要原因。作为专性寄生虫，它们也严重依赖宿主细胞机制来繁殖自己的生命周期。然而，令人惊讶的是，我们缺乏对病毒-人复合物的结构和动力学的全面了解，这些复合物促进了细胞中的病毒复制和疾病进展。例如，迄今为止，蛋白质数据库中保存的条目中只有不到0.01%属于由人和病毒组分形成的RNA-蛋白质（RNP）复合物。因此，在拟议的研究中，我们将使用一个综合的结构生物学方法，涉及实验生物化学和理论生物物理技术相结合（包括X射线晶体学，冷冻电子显微镜和分子动力学模拟），通过测定HIV-宿主前体蛋白的高分辨率结构，研究生物化学良好表征的HIV TAR RNA元件和达特蛋白在HIV mRNA翻译起始中的作用。启动复合体。