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

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.