Molecules and Cells

  • 제19권2호
  • /
  • Pages.246-255
  • /
  • 2005
  • /
  • 1016-8478(pISSN)
  • /
  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
권호 표지

Characterization of the Functional Domains of Human Foamy Virus Integrase Using Chimeric Integrases

  • Lee, Hak Sung (Department of Biotechnology and Bet Research Institute, Chung-Ang University) ;
  • Kang, Seung Yi (Department of Biotechnology and Bet Research Institute, Chung-Ang University) ;
  • Shin, Cha-Gyun (Department of Biotechnology and Bet Research Institute, Chung-Ang University)
  • 투고 : 2004.11.09
  • 심사 : 2005.01.05
  • 발행 : 2005.04.30
⟨ 이전 논문 다음 논문 ⟩

초록

Retroviral integrases insert viral DNA into target DNA. In this process they recognize their own DNA specifically via functional domains. In order to analyze these functional domains, we constructed six chimeric integrases by swapping domains between HIV-1 and HFV integrases, and two point mutants of HFV integrase. Chimeric integrases with the central domain of HIV-1 integrase had strand transfer and disintegration activities, in agreement with the idea that the central domain determines viral DNA specificity and has catalytic activity. On the other hand, chimeric integrases with the central domain of HFV integrase did not have any enzymatic activity apart from FFH that had weak disintegration activity, suggesting that the central domain of HFV integrase was defective catalytically or structurally. However, these inactive chimeras were efficiently complemented by the point mutants (D164A and E200A) of HFV integrase, indicating that the central domain of HFV integrase possesses potential enzymatic activity but is not able to recognize viral or target DNA without the help of its homologous N-terminal and C-terminal domains.

키워드

과제정보

연구 과제 주관 기관 : Korea Science and Engineering Foundation

참고문헌

  1. Achong, B. G., Mansell, P. W. A., Epstein, M. A., and Clifford, P. (1971) An unusual virus from a human nasopharyngeal carcinoma. J. Natl. Cancer Inst. 46, 299-307
  2. Ahn, H.-C., Lee, S.-Y., Kim, J.-W., Son, W. S., Shin, C.-G., et al. (2001) Binding aspects of baicalein to HIV-integrase. Mol. Cells 12, 127-130
  3. Appa, R. S., Shin, C.-G., Lee, P., and Chow, S. A. (2001) Role of the nonspecific DNA-binding region and ${\alpha}$ helices within the core domain of retroviral integrase in selecting target DNA sites for integration. J. Biol. Chem. 276, 45848-45855 https://doi.org/10.1074/jbc.M107365200
  4. Beiger, N., Heller, A. E., Stormann, K. D., and Pfaff, E. (2001) Characterization of chimeric enzymes between caprine arthritis-encephalitis virus, maedi-visna virus and human immunodeficiency virus type 1 integrases expressed in Escherichia coli. J. Gen. Virol. 82, 139-148
  5. Brown, P. O., Bowerman, B., Varmus, H. E., and Bishop, J. M. (1989) Retroviral integration: structure of the initial covalent product and its precursor, and a role for the viral IN protein. Proc. Natl. Acad. Sci. USA 86, 2525-2529
  6. Bushman, F. D., Engelman, A., Palmer, I., Wingfield, P., and Craigie, R. (1993) Domains of the integrase protein of human immunodeficiency virus type 1 responsible for polynucleotidyl transfer and zinc binding. Proc. Natl. Natl. Sci. USA 90, 3428-3432
  7. Chow, S. A., Vincent, K. A., Ellison, V., and Brown, P. O. (1992) Reversal of integration and DNA splicing mediated by integrase of human immunodeficiency virus. Science 255, 723-726 https://doi.org/10.1126/science.1738845
  8. Daniel, R., Katz, R. A., and Skalka, A. M. (1999) A role for DNA-PK in retroviral DNA integration. Science 284, 644- 647 https://doi.org/10.1126/science.284.5414.644
  9. Didine, S. L., Resress, J., Jolly, D., and Sandmeyer, S. B. (1998) A chimeric Ty3/Moloney murine leukemia virus integrase protein is activity in vivo. J. Virol. 72, 4297-4307
  10. Ellison, V. and Brown, P. O. (1994) A stable complex between integrase and viral DNA ends mediates HIV integration in vitro. Proc. Natl. Acad. Sci. USA 91, 7316-7320
  11. Ellison, V., Gerton, J., Vincent, K. A., and Brown, P. O. (1995) An essential interaction between distinct domains of HIV-1 integrase mediates assembly of active multimer. J. Biol. Chem. 270, 3320-3326 https://doi.org/10.1074/jbc.270.7.3320
  12. Engelman, A. and Craigie, R. (1992) Identification of conserved amino acid residues critical for human immunodeficiency virus type 1 integrase function in vitro. J. Virol. 66, 6361-6369
  13. Engelman, A., Mizuuchi, K., and Craigie, R. (1991) HIV-1 DNA integration: mechanism of viral DNA cleavage and DNA strand transfer. Cell 67, 1211-1221 https://doi.org/10.1016/0092-8674(91)90297-C
  14. Engelman, A., Bushman, F. D., and Craigie, R. (1993) Identification of discrete functional domains of HIV-1 integrase and their organization within an active multimeric complex. EMBO J. 12, 3269-3275
  15. Engelman, A., Hickman, A. B., and Craigie, R. (1994) The core and carboxylterminal domains of the integrase protein of human immunodeficiency virus type 1 each contribute to nonspecific DNA binding. J. Virol. 68, 5911-5917
  16. Flugel, R. M., Rethwilm, A., Maurer, B., and Darai, G. (1987) Nucleotide sequence analysis of the env gene and its flanking regions of the human spumaretrovirus reveals two novel genes. EMBO J. 6, 2077-2084
  17. Fujiwara, T. and Mizuuchi, K. (1988) Retrovial DNA integration: structure of an integration intermediate. Cell 54, 497- 504 https://doi.org/10.1016/0092-8674(88)90071-2
  18. Gerton, J. L., Herschlag, D., and Brown, P. O. (1999) Stereospecificity of reactions catalyzed by HIV-1 integrase. J. Biol. Chem. 274, 33480-33487 https://doi.org/10.1074/jbc.274.47.33480
  19. Horton, R. M., Ho, S. N., Pullen, J. K., Hunt, H. D., Cai, Z., et al. (1993) Gene splicing by overlap extension. Methods Enzymol. 217, 270-279 https://doi.org/10.1016/0076-6879(93)17067-F
  20. Kaplana, G. V. and Goff, S. P. (1993) Genetic analysis of homomeric interaction of human immunodeficiency virus type 1 integrase using the yeast two-hybrid system. Proc. Natl. Acad. Sci. USA 90, 10593-10597
  21. Katzman, M. and Sudol, M. (1995) Mapping domains of retroviral integrase responsible for viral DNA specificity and target site selection by analysis of chimeras between human immunodeficiency virus type 1 and visna virus integrase. J. Virol. 69, 5687-5696
  22. Katzman, M. and Sudol, M. (1996) Non-specific alcoholysis, a novel endonuclease activity of human immunodeficiency virus type 1 and other retroviral integrases. J. Virol. 70, 2598- 2604
  23. Katzman, M. and Sudol, M. (1998) Mapping viral DNA specificity to the central region of integrase by using functional human immunodeficiency virus type 1/visna virus chimeric protein. J. Virol. 72, 1744-1753
  24. Katzman, M., Katz, R. A., Skalka, A. M., and Leis, J. (1989) The avian retroviral integration protein cleaves the terminal sequences of linear viral DNA at the in vivo sites of integration. J. Virol. 63, 5319-5327
  25. Katzman, M., Sudol, M., Pufnock, J. S., Zeto, S., and Skinner, L. M. (2000) Mapping target site selection for the non-specific nuclease activities of retroviral integrase. Virus Res. 66, 87- 100 https://doi.org/10.1016/S0168-1702(99)00126-4
  26. Khan, E., Mack, J. P. G., Katz, R. A., Kulkosky, J., and Skalka, A. M. (1991) Retroviral integrase domains: DNA binding and the recognition of LTR sequence. Nucleic Acids Res. 19, 851-860 https://doi.org/10.1093/nar/19.4.851
  27. Kim, J.-H., Choi, H.-K., Lee, H., Park, H. Y., Kim, J.-H., et al. (2004) Novel and recurrent mutations of the LDL receptor gene in Korean patients with familial hypercholesterolemia. Mol. Cells 18, 63-70
  28. Kulkosky, J., Jones, K. S., Katz, R. A., Mack, J. P. G., and Skalka, A. M. (1992) Residues critical for retroviral integrative recombination in a region that is highly conserved among retroviral/retrotransposon integrases and bacterial insertion sequence transposases. Mol. Cell. Biol. 12, 2331- 2338
  29. Leavitt, A. D., Shiue, L., and Varmus, H. E. (1993) Site directed mutagenesis of HIV-1 integrase demonstrates differential effects on integrase functions in vitro. J. Biol. Chem. 268, 2113-2119
  30. Lodi, P. J., Ernst, J. A., Kuszewski, J., Hickman, A. B., Engelman, A., et al. (1995) Solution structure of the DNA binding domain of HIV-1 integrase. Biochemistry 34, 9826-9833 https://doi.org/10.1021/bi00031a002
  31. Lutzke, R. A., Vink, C., and Plasterk, R. H. A. (1994) Characterization of the minimal DNA-binding domain of HIV integrase protein. Nucleic Acids Res. 22, 4125-4131 https://doi.org/10.1093/nar/22.20.4125
  32. Mizuuchi, K. (1992) Polynucleotidyl transfer reaction in transpositoinal DNA recombination. Annu. Rev. Biochem. 61, 1011-1051 https://doi.org/10.1146/annurev.bi.61.070192.005051
  33. Oh, Y.-T. and Shin, C.-G. (1999) Comparison of enzymatic activities of the HIV-1 and HFV integrases to their U5 LTR substrates. Biol. Mol. Biol. Int. 612-629
  34. Pahl, A. and Flugel, R. M. (1993) Endonucleolytic cleavages and DNA-joining activities of the integration protein of human foamy virus. J. Virol. 67, 5426-5434
  35. Pahl, A. and Flugel, R. M. (1995) Characterization of the human spuma retrovirus intgrase by site-directed nutadenesis, complementation analysis, and by swapping the zinc finger domain of HIV-1. J. Biol. Chem. 270, 2957-2966 https://doi.org/10.1074/jbc.270.7.2957
  36. Puras-Lutzke, R. A., Vink, C., and Plasterk, R. H. A. (1994) Characterization of the minimal DNA-binding domain of HIV integrase protein. Nucleic Acids Res. 22, 4125-4131 https://doi.org/10.1093/nar/22.20.4125
  37. Rice, P., Craigie, R., and Davies, D. R. (1996) Retroviral integrases and their cousins. Curr. Opin. Struct. Biol. 6, 76-83 https://doi.org/10.1016/S0959-440X(96)80098-4
  38. Schauer, M. and Billich, A. (1992) The N-terminal region of HIV-1 integrase is required for integration, but for DNA binding. Biochem. Biophys. Res. Commun. 185, 874-880 https://doi.org/10.1016/0006-291X(92)91708-X
  39. Shibagaki, Y. and Chow, S. A. (1997) Central core domain of retroviral integrase is responsible for target site selection. J. Biol. Chem. 272, 8361-8369 https://doi.org/10.1074/jbc.272.13.8361
  40. Shibagaki, Y., Holmes, M. L., Appa, R. S., and Chow, S. A. (1997) Characterization of feline human immunodeficiency virus type 1 integrase and analysis of functional domains. Virology 230, 1-10 https://doi.org/10.1006/viro.1997.8466
  41. Shin, C.-G., Taddeo, B., Haseltine, W. A., and Farnet, C. F. (1994) Genetic analysis of the human immunodeficiency virus type 1 integrase protein. J. Virol. 68, 1633-1642
  42. Tasara, T., Amacker, M., and Hubscher, U. (1999) Intramolecular chimeras of the p51 subunit between HIV-1 and FIV reverse transcriptase suggest a stabilizing function for the p66 subunit in the heterodimeric enzyme. J .Virol. 70, 8277-8284
  43. Van den Ent, F. M., Vos, A., and Plasterk, R. H. A. (1999) Dissecting the role of the N-terminal domain of human immunodeficiency virus integrase by trans-complementation analysis. J. Virol. 73, 3176-3183
  44. Van Gent, D., Vink, C., Groeneger, A. A., and Plasterk, R. H. (1993) Complementation between HIV integrase proteins mutated in different domains. EMBO J. 12, 3261- 3267
  45. Vincent, K. A., Ellison, V., Chow, S. A., and Brown, P. O. (1993) Characterization of human immunodeficiency virus type 1 integrase expressed in Escherichia coli and analysis of variants with amino-terminal mutation. J. Virol. 67, 425-437
  46. Vink, C., Oude Groeneger, A. M., and Plasterk, R. H. (1993) Identification of the catalytic and DNA-binding region of the human immunodeficiency virus type 1 integrase protein. Nucleic Acids Res. 21, 1419-1425 https://doi.org/10.1093/nar/21.6.1419
  47. Woerner, A. M., Klutch, M., Levin, J. G., and Markus-Sekura, C. J. (1992) Localization of DNA binding activity of HIV-1 integrase to the C-terminal half of the protein. AIDS Res. Hum. Retroviruses 8, 2433-2437