Substitutions at Phe61 in the β3-β4 hairpin of HIV-1 reverse transcriptase reveal a role for the fingers subdomain in strand displacement DNA synthesis

Journal of Molecular Biology

Volumn 325, Issue 3, 2003, Pages 443-459

  Fisher, Timothy S ^a   Darden, Tom ^b   Prasad, Vinayaka R ^a  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^b NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES   (United States)

Author keywords

Displacement DNA synthesis; Fingers subdomain; Human immunodeficiency virus; Processivity; Reverse transcriptase

Indexed keywords

DEOXYNUCLEOTIDE TRIPHOSPHATE; DOUBLE STRANDED DNA; NUCLEOTIDE DERIVATIVE; PHENYLALANINE; RNA DIRECTED DNA POLYMERASE; UNCLASSIFIED DRUG; RECOMBINANT PROTEIN; VIRUS DNA;

AMINO ACID SUBSTITUTION; ARTICLE; BASE PAIRING; BINDING SITE; CONTROLLED STUDY; DNA BINDING; DNA STRAND; DNA SYNTHESIS; ENZYME ACTIVITY; HUMAN IMMUNODEFICIENCY VIRUS 1; MUTANT; NONHUMAN; POLYMERIZATION; PRIORITY JOURNAL; WILD TYPE; ANIMAL; BIOSYNTHESIS; CHEMICAL STRUCTURE; CHEMISTRY; CONFORMATION; DNA REPLICATION; DNA TEMPLATE; GENETICS; HUMAN; METABOLISM; MOLECULAR GENETICS; NUCLEOTIDE SEQUENCE; PHENOTYPE; PROTEIN SECONDARY STRUCTURE; PROTEIN TERTIARY STRUCTURE; TIME;

HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1;

AMINO ACID SUBSTITUTION; ANIMALS; BASE SEQUENCE; DNA REPLICATION; DNA, VIRAL; HIV-1 REVERSE TRANSCRIPTASE; HUMANS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; NUCLEIC ACID CONFORMATION; PHENOTYPE; PHENYLALANINE; PROTEIN STRUCTURE, SECONDARY; PROTEIN STRUCTURE, TERTIARY; RECOMBINANT PROTEINS; TEMPLATES, GENETIC; TIME FACTORS;

EID: 0037229160     PISSN: 00222836     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0022-2836(02)01225-1     Document Type: Article

References (52)

1. Telesnitsky, A. & Goff, S. P. (1997). Reverse transcriptase and the generation of retroviral DNA. In Retroviruses (Coffin, J. M., Hughes, S. H. & Varmus, H. E., eds), pp. 121-160, Cold Spring Harbor Laboratory Press, Plainview, NY.
2. Le Grice, S. F. J. (1993). Human immunodeficiency virus reverse transcriptase. In Reverse Transcriptase (Skala, A. & Goff, S. P., eds), pp. 163-191, Cold Spring Harbor Laboratory Press, Plainview, NY.
3. Prasad, V. R. & Goff, S. P. (1989). Linker insertion mutagenesis of human immunodeficiency virus reverse transcriptase expressed in bacteria: Definition of the minimal polymerase domain. Proc. Natl. Acad. Sci. USA, 86, 3104-3108.
4. Prasad, V. R. (1993). Genetic analysis of retroviral reverse transcriptase structure. In Reverse Transcriptase (Goff, S. P. & Skalka, A. M., eds), pp. 135-161, Cold Spring Harbor Laboratory Press, Plainview, NY.
5. Kohlstaedt, L. A., Wang, J., Friedman, J. M., Rice, P. A. & Steitz, T. A. (1992). Crystal structure at 3.5 Å resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Science, 256, 1783-1790.
6. Jacobo-Molina, A., Ding, J., Nanni, R. G., Clark, A. D., Jr, Lu, X., Tantillo, C. et al. (1993). Crystal structure of human immunodeficiency virus type 1 reverse transcriptase complexed with double-stranded DNA at 3.0 Å resolution shows bent DNA. Proc. Natl. Acad. Sci. USA, 90, 6320-6324.
7. Wang, J., Smerdon, S. J., Jager, J., Kohlstaedt, L. A., Rice, P. A., Friedman, J. M. & Steitz, T. A. (1994). Structural basis of asymmetry in the human immunodeficiency virus type 1 reverse transcriptase heterodimer. Proc. Natl. Acad. Sci. USA, 91, 7242-7246.
8. Beard, W. A., Stahl, S. J., Kim, H. R., Bebenek, K., Kumar, A., Strub, M. P. et al. (1994). Structure/function studies of human immunodeficiency virus type 1 reverse transcriptase. Alanine scanning mutagenesis of an alpha-helix in the thumb subdomain. J. Biol. Chem. 269, 28091-28097.
9. Bebenek, K., Beard, W. A., Casas-Finet, J. R., Kim, H. R., Darden, T. A., Wilson, S. H. & Kunkel, T. A. (1995). Reduced frameshift fidelity and processivity of HIV-1 reverse transcriptase mutants containing alanine substitutions in helix H of the thumb subdomain. J. Biol. Chem. 270, 19516-19523.
10. Bebenek, K., Beard, W. A., Darden, T. A., Li, L., Prasad, R., Luton, B. A. et al. (1997). A minor groove binding track in reverse transcriptase. Nature Struct. Biol. 4, 194-197.
11. Kew, Y., Olsen, L., Japour, A. & Prasad, V. R. (1998). Insertions into the β3-β4 hairpin loop of HIV-1 reverse transcriptase reveal a role for fingers subdomain in processive polymerization. J. Biol. Chem. 273, 7529-7537.
12. Arion, D., Borokov, G., Gu, Z., Wainberg, M. A. & Parniak, M. A. (1996). The K65R mutation confers increased DNA polymerase processivity to HIV-1 reverse transcriptase. J. Biol. Chem. 271, 19860-19864.
13. Shah, F., Curr, K., Parniak, M., Mitsuya, H. & Prasad, V. R. (2000). Differential influence of nucleoside analog-resistance mutations K65R and L74V on the overall mutation rate of human immunodeficiency virus reverse transcriptase. J. Biol. Chem. 275, 27037-27044.
14. Kim, B., Ayran, J. C., Sagar, S. G., Adman, E. T., Fuller, S. M., Tran, N. H. & Horrigan, J. (1999). New human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) mutants with increased fidelity of DNA synthesis; accuracy, template binding and processivity. J. Biol. Chem. 274, 27666-27673.
15. Kim, B., Hathaway, T. R. & Loeb, L. A. (1998). Fidelity of mutant HIV-1 reverse transcriptases: Interaction with the single-stranded template influences the accuracy of DNA synthesis. Biochemistry, 37, 5831-5839.
16. Larder, B. A. (1993). Inhibitors of HIV reverse tran-scriptase as antiviral agents and drug resistance. In Reverse Transcriptase (Skalka, A. M. & Goff, S. P., eds), pp. 205-222, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
17. Tantillo, C., Ding, J., Jacobo-Molina, A., Nanni, R. G., Boyer, P. L., Hughes, S. H. et al. (1994). Locations of anti-AIDS drug binding sites and resistance mutations in the three-dimensional structure of HIV-1 reverse transcriptase implications for mechanisms of drug inhibition and resistance. J. Mol. Biol. 243, 369-387.
18. Huang, H., Chopra, R. & Harrison, S. C. (1998). Structure of a covalently trapped catalytic complex of HIV-1 reverse transcriptase: Implications for drug resistance. Science, 282, 1669-1675.
19. Boone, L. R. & Skalka, A. M. (1993). Strand displacement synthesis by reverse transcriptase. In Reverse Transcriptase (Skalka, A. M. & Goff, S. P., eds), pp. 119-133.
20. Charneau, P., Mirambeau, G., Roux, P., Paulous, S., Buc, H. & Clavel, F. (1994). HIV-1 reverse transcription: A termination step at the center of the genome. J. Mol. Biol. 241, 651-662.
21. Zennou, V., Petit, C., Guetard, D., Nerhbass, U., Montagnier, L. & Charneau, P. (2000). HIV-1 genome nuclear import is mediated by a central DNA flap. Cell, 101, 173-185.
22. Matson, S. W., Fay, P. J. & Bambara, R. A. (1980). Mechanism of inhibition of the avian myeloblastosis virus deoxyribonucleic acid polymerase by adriamycin. Biochemistry, 19, 2089-2096.
23. Amacker, M., Hottiger, M. & Hubscher, U. (1995). Feline immunodeficiency virus reverse transcriptase: Expression, functional characterization, and reconstitution of the 66- and 51- kilodalton subunits. J. Virol. 69 , 6273-6279.
24. Whiting, S. H. & Champoux, J. J. (1994). Strand displacement synthesis capability of Moloney murine leukemia virus reverse transcriptase. J. Virol. 68, 4747-4758.
25. Huber, H. E., McCoy, J. M., Seehra, J. S. & Richardson, C. C. (1989). Human immunodeficiency virus 1 reverse transcriptase. J. Biol. Chem. 264, 4669-4678.
26. Hottiger, M., Vladimir, N. P., Thimmig, R. L., McHenry, C. & Hubscher, U. (1994). Strand displacement activity of the human immunodeficiency virus type 1 reverse transcriptase heterodimer and its individual subunits. J. Biol. Chem. 269, 986-991.
27. Fuentes, G. M., Rodriguez-Rodriguez, L., Palaniappan, C., Fay, P. J. & Bambara, R. A. (1996). Strand displacement synthesis of the long terminal repeats by HIV reverse transcriptase. J. Biol. Chem. 271, 1966-1971.
28. Kelleher, C. D. & Champoux, J. J. (1998). Characterization of RNA strand displacement synthesis by Moloney murine leukemia virus reverse transcriptase. J. Biol. Chem. 273, 9976.
29. Amacker, M., Hottiger, M., Mossi, R. & Hubscher, U. (1997). HIV-1 nucleocapsid protein and replication protein A influence the strand displacement DNA synthesis of lentiviral reverse transcriptase. Aids, 11, 534-536.
30. Fisher, T. S. & Prasad, V. R. (2002). Substitutions of Phe61 located in the vicinity of template 5′-overhang influence polymerase fidelity and nucleoside analog sensitivity of HIV-1 reverse transcriptase. J. Biol. Chem. 277, 22345-22352.
31. Whiting, S. H. & Champoux, J. J. (1998). Properties of stand displacement synthesis by Moloney murine leukemia virus reverse transcriptase: Mechanistic implications. J. Mol. Biol. 278, 559.
32. Sawaya, M. R., Prasad, R., Wilson, S. H., Kraut, J. & Pelletier, H. (1997). Crystal structures of human DNA polymerase beta complexed with gapped and nicked DNA: Evidence for an induced fit mechanism. Biochemistry, 36, 11205-11215.
33. Gu, Z., Fletcher, R. S., Arts, E. J., Wainberg, M. A. & Parniak, M. A. (1994). The K65R mutant reverse transcriptase of HIV-1 cross-resistant to 2′,3′-dideoxycytidine, 2′,3′-dideoxy-3′-thiacytidine, and 2′,3′-dideoxyinosine shows reduced sensitivity to specific dideoxynucleoside triphosphate inhibitors in vitro. J. Biol. Chem. 269, 28118-28122.
34. Gu, Z., Arts, E. J., Parniak, M. A. & Wainberg, M. A. (1995). Mutated K65R recombinant reverse transcrip-tase of human immunodeficiency virus type 1 shows diminished chain termination in the presence of 2′,3′-dideoxycytidine 5′-triphosphate and other drugs. Proc. Natl. Acad. Sci. USA, 92, 2760-2764.
35. Gu, Z., Salomon, H., Cherrington, J. M., Mulato, A. S., Chen, M. S., Yarchoan, R. et al. (1995). K65R mutation of human immunodeficiency virus type 1 reverse transcriptase encodes cross-resistance to 9-(2-phosphonylmethoxyethyl)adenine. Antimicrob. Agents Chemother. 39, 1888-1891.
36. Wohrl, B. M., Tantillo, C., Arnold, E. & Le Grice, S. F. (1995). An expanded model of replicating human immunodeficiency virus reverse transcriptase. Biochemistry, 34, 5343-5356.
37. Metzger, W., Hermann, T., Schatz, O., Le Grice, S. F. & Heumann, H. (1993). Hydroxyl radical footprint analysis of human immunodeficiency virus reverse transcriptase-template primer complexes. Proc. Natl. Acad. Sci. USA, 90, 5909-5913.
38. Patel, P. H., Jacobo-Molina, A., Ding, J., Tantillo, C., Clark, D. A., Raag, R. et al. (1995). Insights into DNA polymerization mechanisms from structure and function analysis of HIV-1 reverse transcriptase. Biochemistry, 34, 5351-5363.
39. Tong, W., Lu, C. D., Sharma, S. K., Matsuura, S., So, A. G. & Scott, W. A. (1997). Nucleotide-induced stable complex formation by HIV-1 reverse transcriptase. Biochemistry, 36, 5749-5757.
40. Peletskaya, E. N., Boyer, P. L., Kogon, A. A., Clark, P., Kroth, H., Sayer, J. M. et al. (2001). Cross-linking of the fingers subdomain of human immunodeficiency virus type 1 reverse transcriptase to template-primer. J. Virol. 75, 9435-9445.
41. Lavigne, M. & Buc, H. (1999). Compression of the DNA minor groove is responsible for termination of DNA synthesis by HIV-1 reverse transcriptase. J. Mol. Biol. 285, 977.
42. Winshell, J. & Champoux, J. J. (2001). Structural alterations in the DNA ahead of the primer terminus during displacement synthesis by reverse transcriptases. J. Mol. Biol. 306, 931-943.
43. Lohman, T. M. & Bjornson, K. P. (1996). Mechanisms of helicase-catalyzed DNA unwinding. Annu. Rev. Biochem. 65, 169-214.
44. Shamoo, Y., Friedman, A. M., Parsons, M. R., Konigsberg, W. H. & Steitz, T. A. (1995). Crystal structure of a replication fork single-stranded DNA binding protein (T4 gp32) complexed to DNA. Nature, 376, 362-366.
45. Bochkarev, A., Pfuetzner, R. A., Edwards, A. M. & Frappier, L. (1997). Structure of the single-stranded-DNA-binding domain of replication protein A bound to DNA. Nature, 385, 176-181.
46. Hollis, T., Stattel, J. M., Walther, D. S., Richardson, C. C. & Ellenberger, T. (2001). Structure of the gene 2.5 protein, a single-stranded DNA binding protein encoded by bacteriophage T7. Proc. Natl. Acad. Sci. USA, 98, 9557-9562.
47. Boyer, P. L., Ferris, A. L. & Hughes, S. H. (1992). Casette mutagenesis of the reverse transcriptase of human immunodeficiency virus type 1. J. Virol. 66, 1031-1039.
48. Kew, Y., Song, Q. & Prasad, V. (1994). Subunit selective mutagenesis of Glu89 residue in human immunodeficiency virus reverse transcriptase. J. Biol. Chem. 269, 15331-15336.
49. Feinberg, M. B., Baltimore, D. & Frankel, A. D. (1991). The role of Tat in the human immuno-deficiency virus life cycle indicates a primary effect on transcriptional elongation. Proc. Natl. Acad. Sci. USA, 88, 4045-4049.
50. Arts, E. J., Li, X., Gu, Z., Kleiman, L., Parniak, M. A. & Wainberg, M. A. (1994). Comparison of deoxyoligonucleotide and tRNA(Lys-3) as primers in an endogenous human immunodeficiency virus-1 in vitro reverse transcription/template-switching reaction. J. Biol. Chem. 269, 14672-14680.
51. Kraulis, P. J. (1991). MOLSCRIPT: A program to produce both detailed and schematic plots of protein structures. J. Appl. Crystallog. 24, 946-950.
52. Merritt, E. A. & Bacon, D. J. (1997). Raster3D: Photo-realistic molecular graphics. In Macromolecular Crystallography (Carter, C. W. Jr, ed.), vol. 277, pp. 505-524, Academic Press, New York.