Abstract
The HIV-1 viral protein R (Vpr) is incorporated into virus particle during budding suggesting that its presence in the mature virion is required in the early steps of the virus life cycle in newly infected cells. Vpr is released into the host cell cytoplasm to participate to the translocation of the preintegration complex (PIC) into the nucleus for integration of the viral DNA into the host genome. Actually, Vpr plays a key role in the activation of the transcription of the HIV-1 long terminal repeat (LTR), mediates cell cycle arrest in G2 to M transition, facilitates apoptosis and controls the fidelity of reverse transcription. Moreover, Vpr drives the repair enzyme uracil DNA glycosylase (UNG2) towards degradation. UNG2 has a major role in “Base excision repair” (BER) whose main function is to maintain genome integrity by controlling DNA uracilation. The interaction of Vpr with the cellular protein UNG2 is a key event in various stages of retroviral replication and its role remains to be defined. We have performed the structural study of UNG2 by NMR and we report its (1HN, 15N, 13Cα, 13Cβ and 13C′) chemical shift backbone assignment and its secondary structure in solution as predicted by TALOS-N. We aim to determine with accuracy by NMR, the residues of UNG2 interacting with Vpr, characterize their interaction and use the local structure of UNG2 and its interface with Vpr to propose potential ligands disturbing this interaction.
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Acknowledgements
We would like to thank the TGIR-RMN program for the financial support. Thanks a lot to Dr. François-Xavier Canterelle at Lille University and to Dr. Nelly Morellet at ISCN institute at Gif-sur-Yvette for their help during the recording of the experiments and for their technical advices. We also thank Dr. Nathalie Chazal at UMR 9004 CNRS-Université Montpellier, for the UNG2 (93-313) Plasmid construction.
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Kara, H., Ponchon, L. & Bouaziz, S. Backbone resonance assignment of the human uracil DNA glycosylase-2. Biomol NMR Assign 12, 37–42 (2018). https://doi.org/10.1007/s12104-017-9776-1
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DOI: https://doi.org/10.1007/s12104-017-9776-1