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Characterization of association of human mitochondrial lysyl-tRNA synthetase with HIV-1 Pol and tRNA 3 Lys .
- Source :
-
BMC biochemistry [BMC Biochem] 2018 Mar 21; Vol. 19 (1), pp. 2. Date of Electronic Publication: 2018 Mar 21. - Publication Year :
- 2018
-
Abstract
- Background: An important step in human immunodeficiency virus type 1 (HIV-1) replication is the packaging of tRNA <subscript>3</subscript> <superscript>Lys</superscript> from the host cell, which plays the role of primer RNA in the process of initiation of reverse transcription. The viral GagPol polyprotein precursor, and the human mitochondrial lysyl-tRNA synthetase (mLysRS) from the host cell, have been proposed to be involved in the packaging process. More specifically, the catalytic domain of mLysRS is supposed to interact with the transframe (TF or p6*) and integrase (IN) domains of the Pol region of the GagPol polyprotein.<br />Results: In this work, we report a quantitative characterization of the protein:protein interactions between mLysRS and its viral partners, the Pol polyprotein, and the isolated integrase and transframe domains of Pol. A dissociation constant of 1.3 ± 0.2 nM was determined for the Pol:mLysRS interaction, which exemplifies the robustness of this association. The protease and reverse transcriptase domains of GagPol are dispensable in this association, but the TF and IN domains have to be connected by a linker polypeptide to recapitulate a high affinity partner for mLysRS. The binding of the viral proteins to mLysRS does not dramatically enhance the binding affinity of mLysRS for tRNA <subscript>3</subscript> <superscript>Lys</superscript> .<br />Conclusions: These data support the conclusion that the complex formed between GagPol, mLysRS and tRNA <subscript>3</subscript> <superscript>Lys</superscript> , which involves direct interactions between the IN and TF domains of Pol with mLysRS, is more robust than suggested by the previous models supposed to be involved in the packaging of tRNA <subscript>3</subscript> <superscript>Lys</superscript> into HIV-1 particles.
- Subjects :
- Animals
Catalytic Domain
HIV-1 physiology
Humans
Protein Binding
Protein Processing, Post-Translational
Virus Assembly
pol Gene Products, Human Immunodeficiency Virus genetics
HIV-1 enzymology
Lysine-tRNA Ligase metabolism
Mitochondria enzymology
RNA, Transfer, Lys metabolism
pol Gene Products, Human Immunodeficiency Virus metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1471-2091
- Volume :
- 19
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- BMC biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 29562886
- Full Text :
- https://doi.org/10.1186/s12858-018-0092-x