The HIV-1 Integrase C-Terminal domain induces TAR RNA structural changes promoting Tat binding
2021
Rocchi, Cecilia | Louvat, Camille | Miele, Adriana | Batisse, Julien | Guillon, Christophe | Ballut, Lionel | Lener, Daniela | Negroni, Matteo | RUFF, Marc | Gouet, Patrice | Fiorini, Francesca
Recent evidence indicated that HIV-1 Integrase (IN) binds genomic viral RNA (gRNA) playing a critical role in viral particle morphogenesis and gRNA stability in host cells. Combining biophysical and biochemical approaches we show that the C-terminal flexible 18-residues tail of IN acts as a sensor of the peculiar apical structure of trans-activation response element RNA (TAR), directly interacting with its hexaloop. We highlighted how the whole IN C-terminal domain, once bound to TAR, can change its structure assisting the binding of Tat, the HIV trans-activator protein, which finally displaces IN from TAR. Our results are consistent with the emerging role of IN in early stage of proviral transcription and suggest new steps of HIV-1 life cycle that can be considered as therapeutic targets.
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تم تزويد هذا السجل من قبل Institut national de la recherche agronomique
