Reverse Transcriptase of Human Immunodeficiency Virus Type 1: Functionality of Subunits of the Heterodimer in DNA Synthesis

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 1992 May 1

PMID 1373206

Citations 32

Authors

Z Hostomsky

Z Hostomska

T B Fu

J Taylor

Affiliations

Soon will be listed here.

Abstract

From an in vitro analysis of the DNA-synthesizing abilities of certain specifically mutated forms of the heterodimeric reverse transcriptase of human immunodeficiency virus type 1, we can conclude that in a heterodimer, the functionality of p66 is necessary while the functionality of the p51 subunit is not needed. Conversely, p51 is not able to catalyze DNA synthesis when associated with p66, and yet when the p66 protein is absent, p51 can function. These conclusions applied to DNA synthesis on heteropolymeric RNA and DNA templates.

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References

Lightfoote M, Coligan J, Folks T, Fauci A, Martin M, Venkatesan S . Structural characterization of reverse transcriptase and endonuclease polypeptides of the acquired immunodeficiency syndrome retrovirus. J Virol. 1986; 60(2):771-5. PMC: 288955. DOI: 10.1128/JVI.60.2.771-775.1986. View

Hu S, Court D, ZWEIG M, LEVIN J . Murine leukemia virus pol gene products: analysis with antisera generated against reverse transcriptase and endonuclease fusion proteins expressed in Escherichia coli. J Virol. 1986; 60(1):267-74. PMC: 253925. DOI: 10.1128/JVI.60.1.267-274.1986. View

Hostomsky Z, Appelt K, Ogden R . High-level expression of self-processed HIV-1 protease in Escherichia coli using a synthetic gene. Biochem Biophys Res Commun. 1989; 161(3):1056-63. DOI: 10.1016/0006-291x(89)91350-8. View

Restle T, Muller B, Goody R . Dimerization of human immunodeficiency virus type 1 reverse transcriptase. A target for chemotherapeutic intervention. J Biol Chem. 1990; 265(16):8986-8. View

Mizrahi V, Usdin M, Harington A, Dudding L . Site-directed mutagenesis of the conserved Asp-443 and Asp-498 carboxy-terminal residues of HIV-1 reverse transcriptase. Nucleic Acids Res. 1990; 18(18):5359-63. PMC: 332210. DOI: 10.1093/nar/18.18.5359. View

Wu J, Warren T, Adams J, Proudfoot J, Skiles J, Raghavan P . A novel dipyridodiazepinone inhibitor of HIV-1 reverse transcriptase acts through a nonsubstrate binding site. Biochemistry. 1991; 30(8):2022-6. DOI: 10.1021/bi00222a003. View

Hostomska Z, Matthews D, Davies 2nd J, Nodes B, Hostomsky Z . Proteolytic release and crystallization of the RNase H domain of human immunodeficiency virus type 1 reverse transcriptase. J Biol Chem. 1991; 266(22):14697-702. View

Di Marzo Veronese F, Copeland T, Devico A, Rahman R, Oroszlan S, Gallo R . Characterization of highly immunogenic p66/p51 as the reverse transcriptase of HTLV-III/LAV. Science. 1986; 231(4743):1289-91. DOI: 10.1126/science.2418504. View

Larder B, Purifoy D, Powell K, Darby G . Site-specific mutagenesis of AIDS virus reverse transcriptase. Nature. 1987; 327(6124):716-7. DOI: 10.1038/327716a0. View

10.

Muller B, Restle T, Weiss S, Gautel M, Sczakiel G, Goody R . Co-expression of the subunits of the heterodimer of HIV-1 reverse transcriptase in Escherichia coli. J Biol Chem. 1989; 264(24):13975-8. View

11.

Goff S . Retroviral reverse transcriptase: synthesis, structure, and function. J Acquir Immune Defic Syndr (1988). 1990; 3(8):817-31. View

12.

Cheng N, Painter G, Furman P . Crosslinking of substrates occurs exclusively to the p66 subunit of heterodimeric HIV-1 reverse transcriptase. Biochem Biophys Res Commun. 1991; 174(2):785-9. DOI: 10.1016/0006-291x(91)91486-v. View

13.

Hostomsky Z, Hostomska Z, Hudson G, Moomaw E, Nodes B . Reconstitution in vitro of RNase H activity by using purified N-terminal and C-terminal domains of human immunodeficiency virus type 1 reverse transcriptase. Proc Natl Acad Sci U S A. 1991; 88(4):1148-52. PMC: 50974. DOI: 10.1073/pnas.88.4.1148. View

14.

Davies 2nd J, Hostomska Z, Hostomsky Z, Jordan S, Matthews D . Crystal structure of the ribonuclease H domain of HIV-1 reverse transcriptase. Science. 1991; 252(5002):88-95. DOI: 10.1126/science.1707186. View

15.

Le Grice S, Naas T, Wohlgensinger B, Schatz O . Subunit-selective mutagenesis indicates minimal polymerase activity in heterodimer-associated p51 HIV-1 reverse transcriptase. EMBO J. 1991; 10(12):3905-11. PMC: 453128. DOI: 10.1002/j.1460-2075.1991.tb04960.x. View

16.

Huber H, McCoy J, Seehra J, Richardson C . Human immunodeficiency virus 1 reverse transcriptase. Template binding, processivity, strand displacement synthesis, and template switching. J Biol Chem. 1989; 264(8):4669-78. View