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Article Dans Une Revue Viruses Année : 2020

How HIV-1 Integrase Associates with Human Mitochondrial Lysyl-tRNA Synthetase

Résumé

Replication of human immunodeficiency virus type 1 (HIV-1) requires the packaging of tRNALys,3 from the host cell into the new viral particles. The GagPol viral polyprotein precursor associates with mitochondrial lysyl-tRNA synthetase (mLysRS) in a complex with tRNALys, an essential step to initiate reverse transcription in the virions. The C-terminal integrase moiety of GagPol is essential for its association with mLysRS. We show that integrases from HIV-1 and HIV-2 bind mLysRS with the same efficiency. In this work, we have undertaken to probe the three-dimensional (3D) architecture of the complex of integrase with mLysRS. We first established that the C-terminal domain (CTD) of integrase is the major interacting domain with mLysRS. Using the pBpa-photo crosslinking approach, inter-protein cross-links were observed involving amino acid residues located at the surface of the catalytic domain of mLysRS and of the CTD of integrase. In parallel, using molecular docking simulation, a single structural model of complex was found to outscore other alternative conformations. Consistent with crosslinking experiments, this structural model was further probed experimentally. Five compensatory mutations in the two partners were successfully designed which supports the validity of the model. The complex highlights that binding of integrase could stabilize the tRNALys:mLysRS interaction.

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Virologie
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Dates et versions

hal-03417104 , version 1 (05-11-2021)

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Xaysongkhame Phongsavanh, Noha Al-Qatabi, Mohammed Samer Shaban, Fawzi Khoder-Agha, Merwan El Asri, et al.. How HIV-1 Integrase Associates with Human Mitochondrial Lysyl-tRNA Synthetase. Viruses, 2020, 12 (10), pp.1202. ⟨10.3390/v12101202⟩. ⟨hal-03417104⟩
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