Differential assembly of Rous sarcoma virus tetrameric and octameric intasomes is regulated by the C-terminal domain and tail region of integrase.

Autor:	Bera S; From the Department of Molecular Microbiology and Immunology, Institute for Molecular Virology, Saint Louis University Health Sciences Center, Saint Louis, Missouri 63104 and., Pandey KK; From the Department of Molecular Microbiology and Immunology, Institute for Molecular Virology, Saint Louis University Health Sciences Center, Saint Louis, Missouri 63104 and., Aihara H; the Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455., Grandgenett DP; From the Department of Molecular Microbiology and Immunology, Institute for Molecular Virology, Saint Louis University Health Sciences Center, Saint Louis, Missouri 63104 and Duane.Grandgenett@health.slu.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2018 Oct 19; Vol. 293 (42), pp. 16440-16452. Date of Electronic Publication: 2018 Sep 05.
DOI:	10.1074/jbc.RA118.004768
Abstrakt:	Retrovirus integrase (IN) catalyzes the concerted integration of linear viral DNA ends into chromosomes. The atomic structures of five different retrovirus IN-DNA complexes, termed intasomes, have revealed varying IN subunit compositions ranging from tetramers to octamers, dodecamers, and hexadecamers. Intasomes containing two IN-associated viral DNA ends capable of concerted integration are termed stable synaptic complexes (SSC), and those formed with a viral/target DNA substrate representing the product of strand-transfer reactions are strand-transfer complexes (STC). Here, we investigated the mechanisms associated with the assembly of the Rous sarcoma virus SSC and STC. C-terminal truncations of WT IN (286 residues) indicated a role of the last 18 residues ("tail" region) in assembly of the tetrameric and octameric SSC, physically stabilized by HIV-1 IN strand-transfer inhibitors. Fine mapping through C-terminal truncations and site-directed mutagenesis suggested that at least three residues (Asp-268-Thr-270) past the last β-strand in the C-terminal domain (CTD) are necessary for assembly of the octameric SSC. In contrast, the assembly of the octameric STC was independent of the last 18 residues of IN. Single-site substitutions in the CTD affected the assembly of the SSC, but not necessarily of the STC, suggesting that STC assembly may depend less on specific interactions of the CTD with viral DNA. Additionally, we demonstrate that trans-communication between IN dimer-DNA complexes facilitates the association of native long-terminal repeat (LTR) ends with partially defective LTR ends to produce a hybrid octameric SSC. The differential assembly of the tetrameric and octameric SSC improves our understanding of intasomes. (© 2018 Bera et al.)
Databáze:	MEDLINE
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