NIH R01 · 2025
Structural understanding of the HIV-1 reverse transcription initiation process
Abstract In retroviruses, reverse transcription is initiated from an intermolecular duplex primer formed by nucleocapsid-driven annealing of the U5-primer binding site (U5-PBS) region of the genome with a host tRNA. However, the structure of this critical complex, and how reverse transcriptase (RT) interacts with it is largely unknown. The structure of the HIV-1 complex presented in this proposal shows that four tandem GNRA modules in U5-PBS spatially organizes the complex by making continuous tetraloop-receptor docking interactions: one engages a rearranged tRNA, one sequesters the initiation site, and two sequester the 18-bp primer to inhibit RT binding. Thus, in contrast to the widely…
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