Characterization of association of human mitochondrial lysyl-tRNA synthetase with HIV-1 Pol and tRNA3Lys
Tóm tắt
An important step in human immunodeficiency virus type 1 (HIV-1) replication is the packaging of tRNA3Lys 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. 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 tRNA3Lys. These data support the conclusion that the complex formed between GagPol, mLysRS and tRNA3Lys, 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 tRNA3Lys into HIV-1 particles.
Tài liệu tham khảo
Isel C, Ehresmann C, Marquet R. Initiation of HIV reverse transcription. Viruses. 2010;2:213–43.
Abbink TE, Berkhout B. HIV-1 reverse transcription: close encounters between the viral genome and a cellular tRNA. Adv Pharmacol. 2007;55:99–135.
Jiang M, Mak J, Ladha A, Cohen E, Klein M, Rovinski B, Kleiman L. Identification of tRNAs incorporated into wild-type and mutant human immunodeficiency virus type-1. J Virol. 1993;67(6):3246–53.
Pavon-Eternod M, Wei M, Pan T, Kleiman L. Profiling non-lysyl tRNAs in HIV-1. RNA. 2010;16(2):267–73.
Gabor J, Cen S, Javanbakht H, Niu MJ, Kleiman L. Effect of altering the tRNA3 Lys concentration in human immunodeficiency virus type 1 upon its annealing to viral RNA, GagPol incorporation, and viral infectivity. J Virol. 2002;76(18):9096–102.
Cen S, Khorchid A, Javanbakht H, Gabor J, Stello T, Shiba K, Musier-Forsyth K, Kleiman L. Incorporation of lysyl-tRNA synthetase into human immunodeficiency virus type 1. J Virol. 2001;75(11):5043–8.
Kaminska M, Shalak V, Francin M, Mirande M. Viral hijacking of mitochondrial lysyl-tRNA synthetase. J Virol. 2007;81(1):68–73.
Tolkunova E, Park H, Xia J, King MP, Davidson E. The human lysyl-tRNA synthetase gene encodes both the cytoplasmic and mitochondrial enzymes by means of an unusual alternative splicing of the primary transcript. J Biol Chem. 2000;275(45):35063–9.
Guo M, Ignatov M, Musier-Forsyth K, Schimmel P, Yang XL. Crystal structure of tetrameric form of human lysyl-tRNA synthetase: implications for multisynthetase complex formation. Proc Natl Acad Sci U S A. 2008;105(7):2331–6.
Francin M, Kaminska M, Kerjan P, Mirande M. The N-terminal domain of mammalian lysyl-tRNA synthetase is a functional tRNA-binding domain. J Biol Chem. 2002;277(3):1762–9.
Francin M, Mirande M. Functional dissection of the eukaryotic-specific tRNA-interacting factor of lysyl-tRNA synthetase. J Biol Chem. 2003;278(3):1472–9.
Dias J, Octobre G, Kobbi L, Comisso M, Flisiak S, Mirande M. Activation of human mitochondrial lysyl-tRNA synthetase upon maturation of its premitochondrial precursor. Biochemistry. 2012;51(4):909–16.
Mirande M. The aminoacyl-tRNA Synthetase complex. Subcell Biochem. 2017;83:505–22.
Rémion A, Khoder-Agha F, Cornu D, Argentini M, Redeker V, Mirande M. Identification of protein interfaces within the multi-aminoacyl-tRNA synthetase complex: the case of lysyl-tRNA synthetase and the scaffold protein p38. FEBS Open Bio. 2016;6:696–706.
Quevillon S, Robinson JC, Berthonneau E, Siatecka M, Mirande M. Macromolecular assemblage of aminoacyl-tRNA synthetases: identification of protein-protein interactions and characterization of a core protein. J Mol Biol. 1999;285(1):183–95.
Sundquist WI, Kräusslich HG. HIV-1 assembly, budding, and maturation. Cold Spring Harb Perspect Med. 2012;2:a006924.
Kobbi L, Octobre G, Dias J, Comisso M, Mirande M. Association of mitochondrial lysyl-tRNA synthetase with HIV-1 GagPol involves catalytic domain of the synthetase and transframe and integrase domains of pol. J Mol Biol. 2011;410(5):875–86.
Kobbi L, Dias J, Comisso M, Mirande M. Association of human mitochondrial lysyl−tRNA synthetase with HIV−1 GagPol does not require other viral proteins. Biochimie Open. 2016;2:52–61.
Kovaleski BJ, Kennedy R, Hong MK, Datta SA, Kleiman L, Rein A, Musier-Forsyth K. In vitro characterization of the interaction between HIV-1 gag and human lysyl-tRNA synthetase. J Biol Chem. 2006;281(28):19449–56.
Dewan V, Wei M, Kleiman L, Musier-Forsyth K. Dual role for motif 1 residues of human lysyl-tRNA synthetase in dimerization and packaging into HIV-1. J Biol Chem. 2012;287(50):41955–62.
Whitmore L, Wallace BA. Protein secondary structure analyses from circular dichroism spectroscopy: methods and reference databases. Biopolymers. 2008;89(5):392–400.
Degorce F, Card A, Soh S, Trinquet E, Knapik GP, Xie B. HTRF: a technology tailored for drug discovery - a review of theoretical aspects and recent applications. Curr Chem Genomics. 2009;3:22–32.
Robinson JC, Kerjan P, Mirande M. Macromolecular assemblage of aminoacyl-tRNA synthetases: quantitative analysis of protein-protein interactions and mechanism of complex assembly. J Mol Biol. 2000;304(5):983–94.
Pornillos O, Ganser-Pornillos BK, Yeager M. Atomic-level modelling of the HIV capsid. Nature. 2011;469(7330):424–7.
Kovaleski BJ, Kennedy R, Khorchid A, Kleiman L, Matsuo H, Musier-Forsyth K. Critical role of helix 4 of HIV-1 capsid C-terminal domain in interactions with human lysyl-tRNA synthetase. J Biol Chem. 2007;282(44):32274–9.
Mak J, Jiang M, Wainberg MA, Hammarskjöld ML, Rekosh D, Kleiman L. Role of Pr160Gag-pol in mediating the selective incorporation of tRNALys into human immunodeficiency virus type 1 particles. J Virol. 1994;68(4):2065–72.
Leavitt AD, Robles G, Alesandro N, Varmus HE. Human immunodeficiency virus type 1 integrase mutants retain in vitro integrase activity yet fail to integrate viral DNA efficiently during infection. J Virol. 1996;70(2):721–8.
Zhu K, Dobard C, Chow SA. Requirement for integrase during reverse transcription of human immunodeficiency virus type 1 and the effect of cysteine mutations of integrase on its interactions with reverse transcriptase. J Virol. 2004;78(10):5045–55.
Kessl JJ, Kutluay SB, Townsend D, Rebensburg S, Slaughter A, Larue RC, Shkriabai N, Bakouche N, Fuchs JR, Bieniasz PD, et al. HIV-1 integrase binds the viral RNA genome and is essential during virion morphogenesis. Cell. 2016;166(5):1257–68. e1212
Freed EO. HIV-1 assembly, release and maturation. Nat Rev Microbiol. 2015;13:484–96.
Schur FK, Obr M, Hagen WJ, Wan W, Jakobi AJ, Kirkpatrick JM, Sachse C, Krausslich HG, Briggs JA. An atomic model of HIV-1 capsid-SP1 reveals structures regulating assembly and maturation. Science. 2016;353(6298):506–8.
Beissinger M, Paulus C, Bayer P, Wolf H, Rosch P, Wagner R. Sequence-specific resonance assignments of the 1H-NMR spectra and structural characterization in solution of the HIV-1 transframe protein p6. Eur J Biochem. 1996;237(2):383–92.
Bonnefond L, Castro de Moura M, Ribas de Pouplana L, Nureki O. Crystal structures of Entamoeba histolytica lysyl-tRNA synthetase reveal conformational changes upon lysine binding and a specific helix bundle domain. FEBS Lett. 2014;588(23):4478–86.