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

艾滋病毒等病毒是新发传染病和持续流行的主要原因。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-人类复合体的结构和动力学的全面了解，这些复合体促进了病毒的复制和细胞内的疾病发展。例如，到目前为止保存在蛋白质数据库中的条目中，只有不到0.01%的条目涉及由人类和病毒成分形成的RNA-蛋白质(RNP)复合体。因此，在拟议的研究中，我们将使用一种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(包括X射线结晶学、低温电子显微镜和分子动力学模拟)，通过确定HIV-宿主起始前复合体的高分辨结构，研究生物化学特征良好的HIV TAR RNA元件和TAT蛋白在HIV mRNA翻译起始中的作用。

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.