A C-terminal "Tail" Region in the Rous Sarcoma Virus Integrase Provides High Plasticity of Functional Integrase Oligomerization during Intasome Assembly.
| Autor: | Pandey KK; From the Department of Microbiology and Immunology, Institute for Molecular Virology, Saint Louis University, St. Louis, Missouri 63104 and., Bera S; From the Department of Microbiology and Immunology, Institute for Molecular Virology, Saint Louis University, St. Louis, Missouri 63104 and., Shi K; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455., Aihara H; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455., Grandgenett DP; From the Department of Microbiology and Immunology, Institute for Molecular Virology, Saint Louis University, St. Louis, Missouri 63104 and grandgdp@slu.edu. |
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| Jazyk: | angličtina |
| Zdroj: | The Journal of biological chemistry [J Biol Chem] 2017 Mar 24; Vol. 292 (12), pp. 5018-5030. Date of Electronic Publication: 2017 Feb 08. |
| DOI: | 10.1074/jbc.M116.773382 |
| Abstrakt: | The retrovirus integrase (IN) inserts the viral cDNA into the host DNA genome. Atomic structures of five different retrovirus INs complexed with their respective viral DNA or branched viral/target DNA substrates have indicated these intasomes are composed of IN subunits ranging from tetramers, to octamers, or to hexadecamers. IN precursors are monomers, dimers, or tetramers in solution. But how intasome assembly is controlled remains unclear. Therefore, we sought to unravel the functional mechanisms in different intasomes. We produced kinetically stabilized Rous sarcoma virus (RSV) intasomes with human immunodeficiency virus type 1 strand transfer inhibitors that interact simultaneously with IN and viral DNA within intasomes. We examined the ability of RSV IN dimers to assemble two viral DNA molecules into intasomes containing IN tetramers in contrast to one possessing IN octamers. We observed that the last 18 residues of the C terminus ("tail" region) of IN (residues 1-286) determined whether an IN tetramer or octamer assembled with viral DNA. A series of truncations of the tail region indicated that these 18 residues are critical for the assembly of an intasome containing IN octamers but not for an intasome containing IN tetramers. The C-terminally truncated IN (residues 1-269) produced an intasome that contained tetramers but failed to produce an intasome with octamers. Both intasomes have similar catalytic activities. The results suggest a high degree of plasticity for functional multimerization and reveal a critical role of the C-terminal tail region of IN in higher order oligomerization of intasomes, potentially informing future strategies to prevent retroviral integration. (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.) |
| Databáze: | MEDLINE |
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