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Characterization and targeting the dynamic recognition of Trp37-G during the interaction of NCp7 protein of HIV-1 with nucleic acids

Abstract : Nucleocapsid protein (NC) plays crucial roles in HIV-1 life cycle through its nucleic acid (NA) chaperoning property that involves recognition of it’s Trp37 residue with a Guanine residue of the target nucleic acid sequences. Herein, we characterized this dynamic Trp37-G recognition with sequences involved in reverse transcription and genomic RNA packaging. Using the fluorescent thienoguanosine (thG) and 2-thienyl-3-hydroxychromone (3HCnt) nucleoside analogues, we determined the whole set of kinetic rate constants for annealing of (-)PBS with (+)PBS in the absence and presence of NC. We also investigated the role of NA sugar in NC-RNA and NC-DNA complexes, as NC binds with opposite polarity to DNA and RNA sequences. We confirmed that the interaction of the Trp37 residue with guanines was critical for the formation of complexes with both RNA and DNA variants of PBS and SL3. Finally, we performed screening of NC inhibitors and tested the selected hits on a thG-based assay.
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Rajhans Sharma. Characterization and targeting the dynamic recognition of Trp37-G during the interaction of NCp7 protein of HIV-1 with nucleic acids. Biophysics. Université de Strasbourg, 2018. English. ⟨NNT : 2018STRAJ014⟩. ⟨tel-02918150⟩

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