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. 1994 Dec 20;91(26):12676–12680. doi: 10.1073/pnas.91.26.12676

Propensity for a leucine zipper-like domain of human immunodeficiency virus type 1 gp41 to form oligomers correlates with a role in virus-induced fusion rather than assembly of the glycoprotein complex.

C Wild 1, J W Dubay 1, T Greenwell 1, T Baird Jr 1, T G Oas 1, C McDanal 1, E Hunter 1, T Matthews 1
PMCID: PMC45502  PMID: 7809100

Abstract

For a number of viruses, oligomerization is a critical component of envelope processing and surface expression. Previously, we reported that a synthetic peptide (DP-107) corresponding to the putative leucine zipper region (aa 553-590) of the transmembrane protein (gp41) of human immunodeficiency virus type 1 (HIV-1) exhibited alpha-helical secondary structure and self-associated as a coiled coil. In view of the tendency of this type of structure to mediate protein association, we speculated that this region of gp41 might play a role in HIV-1 envelope oligomerization. However, later it was shown that mutations which should disrupt the structural elements of this region of gp41 did not affect envelope processing, transport, or surface expression (assembly oligomerization). In this report we compare the effects of amino acid substitutions within this coiled-coil region on structure and function of both viral envelope proteins and the corresponding synthetic peptides. Our results establish a correlation between the destabilizing effects of amino acid substitutions on coiled-coil structure in the peptide model and phenotype of virus entry. These biological and physical biochemical studies do not support a role for the coiled-coil structure in mediating the assembly oligomerization of HIV-1 envelope but do imply that this region of gp41 plays a key role in the sequence of events associated with viral entry. We propose a functional role for the coiled-coil domain of HIV-1 gp41.

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Selected References

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

  1. Bosch M. L., Earl P. L., Fargnoli K., Picciafuoco S., Giombini F., Wong-Staal F., Franchini G. Identification of the fusion peptide of primate immunodeficiency viruses. Science. 1989 May 12;244(4905):694–697. doi: 10.1126/science.2541505. [DOI] [PubMed] [Google Scholar]
  2. Britton P. Coronavirus motif. Nature. 1991 Oct 3;353(6343):394–394. doi: 10.1038/353394a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Buckland R., Malvoisin E., Beauverger P., Wild F. A leucine zipper structure present in the measles virus fusion protein is not required for its tetramerization but is essential for fusion. J Gen Virol. 1992 Jul;73(Pt 7):1703–1707. doi: 10.1099/0022-1317-73-7-1703. [DOI] [PubMed] [Google Scholar]
  4. Cao J., Bergeron L., Helseth E., Thali M., Repke H., Sodroski J. Effects of amino acid changes in the extracellular domain of the human immunodeficiency virus type 1 gp41 envelope glycoprotein. J Virol. 1993 May;67(5):2747–2755. doi: 10.1128/jvi.67.5.2747-2755.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carr C. M., Kim P. S. A spring-loaded mechanism for the conformational change of influenza hemagglutinin. Cell. 1993 May 21;73(4):823–832. doi: 10.1016/0092-8674(93)90260-w. [DOI] [PubMed] [Google Scholar]
  6. Chambers P., Pringle C. R., Easton A. J. Heptad repeat sequences are located adjacent to hydrophobic regions in several types of virus fusion glycoproteins. J Gen Virol. 1990 Dec;71(Pt 12):3075–3080. doi: 10.1099/0022-1317-71-12-3075. [DOI] [PubMed] [Google Scholar]
  7. Chen S. S., Lee C. N., Lee W. R., McIntosh K., Lee T. H. Mutational analysis of the leucine zipper-like motif of the human immunodeficiency virus type 1 envelope transmembrane glycoprotein. J Virol. 1993 Jun;67(6):3615–3619. doi: 10.1128/jvi.67.6.3615-3619.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Dalgleish A. G., Chanh T. C., Kennedy R. C., Kanda P., Clapham P. R., Weiss R. A. Neutralization of diverse HIV-1 strains by monoclonal antibodies raised against a gp41 synthetic peptide. Virology. 1988 Jul;165(1):209–215. doi: 10.1016/0042-6822(88)90674-5. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. 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]
  13. Einfeld D., Hunter E. Oligomeric structure of a prototype retrovirus glycoprotein. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8688–8692. doi: 10.1073/pnas.85.22.8688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fisher A. G., Ratner L., Mitsuya H., Marselle L. M., Harper M. E., Broder S., Gallo R. C., Wong-Staal F. Infectious mutants of HTLV-III with changes in the 3' region and markedly reduced cytopathic effects. Science. 1986 Aug 8;233(4764):655–659. doi: 10.1126/science.3014663. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Guiltinan M. J., Marcotte W. R., Jr, Quatrano R. S. A plant leucine zipper protein that recognizes an abscisic acid response element. Science. 1990 Oct 12;250(4978):267–271. doi: 10.1126/science.2145628. [DOI] [PubMed] [Google Scholar]
  17. Kono K., Nishii H., Takagishi T. Fusion activity of an amphiphilic polypeptide having acidic amino acid residues: generation of fusion activity by alpha-helix formation and charge neutralization. Biochim Biophys Acta. 1993 Jun 24;1164(1):81–90. doi: 10.1016/0167-4838(93)90115-8. [DOI] [PubMed] [Google Scholar]
  18. Kowalski M., Bergeron L., Dorfman T., Haseltine W., Sodroski J. Attenuation of human immunodeficiency virus type 1 cytopathic effect by a mutation affecting the transmembrane envelope glycoprotein. J Virol. 1991 Jan;65(1):281–291. doi: 10.1128/jvi.65.1.281-291.1991. [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. 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]
  21. O'Shea E. K., Rutkowski R., Kim P. S. Evidence that the leucine zipper is a coiled coil. Science. 1989 Jan 27;243(4890):538–542. doi: 10.1126/science.2911757. [DOI] [PubMed] [Google Scholar]
  22. Sattentau Q. J., Moore J. P. Conformational changes induced in the human immunodeficiency virus envelope glycoprotein by soluble CD4 binding. J Exp Med. 1991 Aug 1;174(2):407–415. doi: 10.1084/jem.174.2.407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sattentau Q. J., Moore J. P., Vignaux F., Traincard F., Poignard P. Conformational changes induced in the envelope glycoproteins of the human and simian immunodeficiency viruses by soluble receptor binding. J Virol. 1993 Dec;67(12):7383–7393. doi: 10.1128/jvi.67.12.7383-7393.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sattentau Q. J., Weiss R. A. The CD4 antigen: physiological ligand and HIV receptor. Cell. 1988 Mar 11;52(5):631–633. doi: 10.1016/0092-8674(88)90397-2. [DOI] [PubMed] [Google Scholar]
  25. Syu W. J., Lee W. R., Du B., Yu Q. C., Essex M., Lee T. H. Role of conserved gp41 cysteine residues in the processing of human immunodeficiency virus envelope precursor and viral infectivity. J Virol. 1991 Nov;65(11):6349–6352. doi: 10.1128/jvi.65.11.6349-6352.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Vinson C. R., Sigler P. B., McKnight S. L. Scissors-grip model for DNA recognition by a family of leucine zipper proteins. Science. 1989 Nov 17;246(4932):911–916. doi: 10.1126/science.2683088. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Willey R. L., Smith D. H., Lasky L. A., Theodore T. S., Earl P. L., Moss B., Capon D. J., Martin M. A. In vitro mutagenesis identifies a region within the envelope gene of the human immunodeficiency virus that is critical for infectivity. J Virol. 1988 Jan;62(1):139–147. doi: 10.1128/jvi.62.1.139-147.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]

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