Effect of tRNA on the Maturation of HIV-1 Reverse Transcriptase. Issue 13 (22nd June 2018)

• Record Type: Journal Article
• Authors: Ilina, Tatiana V.; Slack, Ryan L.; Elder, John H.; Sarafianos, Stefan G.; Parniak, Michael A.; Ishima, Rieko
• Is Part Of: Journal of molecular biology. Volume 430:Issue 13(2018)
• Page Start: 1891
• Page End: 1900
• Publication Date: 2018-06-22
• Subjects: HIV-1 -- proteolysis -- maturation -- tRNA -- reverse transcriptase -- RNase H; RT reverse transcriptase -- RNH ribonuclease H -- SEC size exclusion chromatography; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2018.02.027
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: The mature HIV-1 reverse transcriptase is a heterodimer that comprises 66 kDa (p66) and 51 kDa (p51) subunits. The latter is formed by HIV-1 protease-catalyzed removal of a C-terminal ribonuclease H domain from a p66 subunit. This proteolytic processing is a critical step in virus maturation and essential for viral infectivity. Here, we report that tRNA significantly enhances in vitro processing even at a substoichiometric tRNA:p66/p66 ratio. Other double-stranded RNAs have considerably less pronounced effect. Our data support a model where interaction of p66/p66 with tRNA introduces conformational asymmetry in the two subunits, permitting specific proteolytic processing of one p66 to provide the mature RT p66/p51 heterodimer. Graphical abstract: Unlabelled Image Highlights: HIV-1 protease-catalyzed processing of premature reverse transcriptase p66 to yield p66/p51 heterodimer was investigated at various conditions in vitro . p66/p66 homodimer is the substrate for HIV-1 protease processing to become a mature p66/p51 heterodimer. tRNA interacts with p66/p66 homodimer and facilitates selective cleavage at the p51-RNH site by HIV-1 protease.