Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1993 Jun;67(6):3615–3619. doi: 10.1128/jvi.67.6.3615-3619.1993

Mutational analysis of the leucine zipper-like motif of the human immunodeficiency virus type 1 envelope transmembrane glycoprotein.

S S Chen 1, C N Lee 1, W R Lee 1, K McIntosh 1, T H Lee 1
PMCID: PMC237711  PMID: 8497069

Abstract

The N-terminal region of the envelope (env) transmembrane protein of human immunodeficiency virus type 1 (HIV-1) has a leucine zipper-like motif. This highly conserved zipper motif, which consists of a heptad repeat of leucine or isoleucine residues, has been suggested to play a role in HIV-1 env glycoprotein oligomerization. This hypothesis was tested by replacing the highly conserved leucine or isoleucine residues in the zipper motif with a strong alpha-helix breaker, proline. We report here that such substitutions did not abolish the ability of env protein to form oligomers, indicating that this highly conserved zipper motif does not have a crucial role in env protein oligomerization. However, the mutant viruses all showed impaired infectivity, suggesting that this conserved zipper motif can have an important role in the virus life cycle.

Full text

PDF
3615

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allan J. S., Coligan J. E., Barin F., McLane M. F., Sodroski J. G., Rosen C. A., Haseltine W. A., Lee T. H., Essex M. Major glycoprotein antigens that induce antibodies in AIDS patients are encoded by HTLV-III. Science. 1985 May 31;228(4703):1091–1094. doi: 10.1126/science.2986290. [DOI] [PubMed] [Google Scholar]
  2. Barin F., McLane M. F., Allan J. S., Lee T. H., Groopman J. E., Essex M. Virus envelope protein of HTLV-III represents major target antigen for antibodies in AIDS patients. Science. 1985 May 31;228(4703):1094–1096. doi: 10.1126/science.2986291. [DOI] [PubMed] [Google Scholar]
  3. Brendel V., Karlin S. Too many leucine zippers? Nature. 1989 Oct 19;341(6243):574–575. doi: 10.1038/341574a0. [DOI] [PubMed] [Google Scholar]
  4. Buckland R., Wild F. Leucine zipper motif extends. Nature. 1989 Apr 13;338(6216):547–547. doi: 10.1038/338547a0. [DOI] [PubMed] [Google Scholar]
  5. Chen S. S., Huang A. S. Further characterization of the vesicular stomatitis virus temperature-sensitive O45 mutant: intracellular conversion of the glycoprotein to a soluble form. J Virol. 1986 Aug;59(2):210–215. doi: 10.1128/jvi.59.2.210-215.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chou P. Y., Fasman G. D. Structural and functional role of leucine residues in proteins. J Mol Biol. 1973 Mar 5;74(3):263–281. doi: 10.1016/0022-2836(73)90372-0. [DOI] [PubMed] [Google Scholar]
  7. Dalgleish A. G., Beverley P. C., Clapham P. R., Crawford D. H., Greaves M. F., Weiss R. A. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984 Dec 20;312(5996):763–767. doi: 10.1038/312763a0. [DOI] [PubMed] [Google Scholar]
  8. Delwart E. L., Mosialos G., Gilmore T. Retroviral envelope glycoproteins contain a "leucine zipper"-like repeat. AIDS Res Hum Retroviruses. 1990 Jun;6(6):703–706. doi: 10.1089/aid.1990.6.703. [DOI] [PubMed] [Google Scholar]
  9. Dubay J. W., Roberts S. J., Brody B., Hunter E. Mutations in the leucine zipper of the human immunodeficiency virus type 1 transmembrane glycoprotein affect fusion and infectivity. J Virol. 1992 Aug;66(8):4748–4756. doi: 10.1128/jvi.66.8.4748-4756.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Earl P. L., Doms R. W., Moss B. Oligomeric structure of the human immunodeficiency virus type 1 envelope glycoprotein. Proc Natl Acad Sci U S A. 1990 Jan;87(2):648–652. doi: 10.1073/pnas.87.2.648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fisher A. G., Feinberg M. B., Josephs S. F., Harper M. E., Marselle L. M., Reyes G., Gonda M. A., Aldovini A., Debouk C., Gallo R. C. The trans-activator gene of HTLV-III is essential for virus replication. 1986 Mar 27-Apr 2Nature. 320(6060):367–371. doi: 10.1038/320367a0. [DOI] [PubMed] [Google Scholar]
  12. Gallaher W. R., Ball J. M., Garry R. F., Griffin M. C., Montelaro R. C. A general model for the transmembrane proteins of HIV and other retroviruses. AIDS Res Hum Retroviruses. 1989 Aug;5(4):431–440. doi: 10.1089/aid.1989.5.431. [DOI] [PubMed] [Google Scholar]
  13. Gnann J. W., Jr, McCormick J. B., Mitchell S., Nelson J. A., Oldstone M. B. Synthetic peptide immunoassay distinguishes HIV type 1 and HIV type 2 infections. Science. 1987 Sep 11;237(4820):1346–1349. doi: 10.1126/science.2888192. [DOI] [PubMed] [Google Scholar]
  14. Klatzmann D., Champagne E., Chamaret S., Gruest J., Guetard D., Hercend T., Gluckman J. C., Montagnier L. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature. 1984 Dec 20;312(5996):767–768. doi: 10.1038/312767a0. [DOI] [PubMed] [Google Scholar]
  15. Kornfeld H., Riedel N., Viglianti G. A., Hirsch V., Mullins J. I. Cloning of HTLV-4 and its relation to simian and human immunodeficiency viruses. Nature. 1987 Apr 9;326(6113):610–613. doi: 10.1038/326610a0. [DOI] [PubMed] [Google Scholar]
  16. Kouzarides T., Ziff E. The role of the leucine zipper in the fos-jun interaction. Nature. 1988 Dec 15;336(6200):646–651. doi: 10.1038/336646a0. [DOI] [PubMed] [Google Scholar]
  17. Kowalski M., Potz J., Basiripour L., Dorfman T., Goh W. C., Terwilliger E., Dayton A., Rosen C., Haseltine W., Sodroski J. Functional regions of the envelope glycoprotein of human immunodeficiency virus type 1. Science. 1987 Sep 11;237(4820):1351–1355. doi: 10.1126/science.3629244. [DOI] [PubMed] [Google Scholar]
  18. Kunkel T. A. Rapid and efficient site-specific mutagenesis without phenotypic selection. Proc Natl Acad Sci U S A. 1985 Jan;82(2):488–492. doi: 10.1073/pnas.82.2.488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Landschulz W. H., Johnson P. F., McKnight S. L. The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins. Science. 1988 Jun 24;240(4860):1759–1764. doi: 10.1126/science.3289117. [DOI] [PubMed] [Google Scholar]
  20. Leucine-zipper motif update. Nature. 1989 Jul 13;340(6229):103–104. doi: 10.1038/340103a0. [DOI] [PubMed] [Google Scholar]
  21. Leucine-zipper motif update. Nature. 1989 Jul 13;340(6229):103–104. doi: 10.1038/340103a0. [DOI] [PubMed] [Google Scholar]
  22. Lifson J. D., Feinberg M. B., Reyes G. R., Rabin L., Banapour B., Chakrabarti S., Moss B., Wong-Staal F., Steimer K. S., Engleman E. G. Induction of CD4-dependent cell fusion by the HTLV-III/LAV envelope glycoprotein. Nature. 1986 Oct 23;323(6090):725–728. doi: 10.1038/323725a0. [DOI] [PubMed] [Google Scholar]
  23. Maddon P. J., Dalgleish A. G., McDougal J. S., Clapham P. R., Weiss R. A., Axel R. The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain. Cell. 1986 Nov 7;47(3):333–348. doi: 10.1016/0092-8674(86)90590-8. [DOI] [PubMed] [Google Scholar]
  24. McDougal J. S., Mawle A., Cort S. P., Nicholson J. K., Cross G. D., Scheppler-Campbell J. A., Hicks D., Sligh J. Cellular tropism of the human retrovirus HTLV-III/LAV. I. Role of T cell activation and expression of the T4 antigen. J Immunol. 1985 Nov;135(5):3151–3162. [PubMed] [Google Scholar]
  25. Owens R. J., Compans R. W. The human immunodeficiency virus type 1 envelope glycoprotein precursor acquires aberrant intermolecular disulfide bonds that may prevent normal proteolytic processing. Virology. 1990 Dec;179(2):827–833. doi: 10.1016/0042-6822(90)90151-g. [DOI] [PubMed] [Google Scholar]
  26. Pinter A., Honnen W. J., Tilley S. A., Bona C., Zaghouani H., Gorny M. K., Zolla-Pazner S. Oligomeric structure of gp41, the transmembrane protein of human immunodeficiency virus type 1. J Virol. 1989 Jun;63(6):2674–2679. doi: 10.1128/jvi.63.6.2674-2679.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Popovic M., Sarngadharan M. G., Read E., Gallo R. C. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science. 1984 May 4;224(4648):497–500. doi: 10.1126/science.6200935. [DOI] [PubMed] [Google Scholar]
  28. Robey W. G., Safai B., Oroszlan S., Arthur L. O., Gonda M. A., Gallo R. C., Fischinger P. J. Characterization of envelope and core structural gene products of HTLV-III with sera from AIDS patients. Science. 1985 May 3;228(4699):593–595. doi: 10.1126/science.2984774. [DOI] [PubMed] [Google Scholar]
  29. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schuermann M., Neuberg M., Hunter J. B., Jenuwein T., Ryseck R. P., Bravo R., Müller R. The leucine repeat motif in Fos protein mediates complex formation with Jun/AP-1 and is required for transformation. Cell. 1989 Feb 10;56(3):507–516. doi: 10.1016/0092-8674(89)90253-5. [DOI] [PubMed] [Google Scholar]
  31. Sodroski J., Goh W. C., Rosen C., Campbell K., Haseltine W. A. Role of the HTLV-III/LAV envelope in syncytium formation and cytopathicity. 1986 Jul 31-Aug 6Nature. 322(6078):470–474. doi: 10.1038/322470a0. [DOI] [PubMed] [Google Scholar]
  32. Turner R., Tjian R. Leucine repeats and an adjacent DNA binding domain mediate the formation of functional cFos-cJun heterodimers. Science. 1989 Mar 31;243(4899):1689–1694. doi: 10.1126/science.2494701. [DOI] [PubMed] [Google Scholar]
  33. Veronese F. D., DeVico A. L., Copeland T. D., Oroszlan S., Gallo R. C., Sarngadharan M. G. Characterization of gp41 as the transmembrane protein coded by the HTLV-III/LAV envelope gene. Science. 1985 Sep 27;229(4720):1402–1405. doi: 10.1126/science.2994223. [DOI] [PubMed] [Google Scholar]
  34. Wang J. J., Steel S., Wisniewolski R., Wang C. Y. Detection of antibodies to human T-lymphotropic virus type III by using a synthetic peptide of 21 amino acid residues corresponding to a highly antigenic segment of gp41 envelope protein. Proc Natl Acad Sci U S A. 1986 Aug;83(16):6159–6163. doi: 10.1073/pnas.83.16.6159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wild C., Oas T., McDanal C., Bolognesi D., Matthews T. A synthetic peptide inhibitor of human immunodeficiency virus replication: correlation between solution structure and viral inhibition. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10537–10541. doi: 10.1073/pnas.89.21.10537. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES