Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1988 Nov;85(22):8688–8692. doi: 10.1073/pnas.85.22.8688

Oligomeric structure of a prototype retrovirus glycoprotein.

D Einfeld 1, E Hunter 1
PMCID: PMC282525  PMID: 2847170

Abstract

The structure of the Rous sarcoma virus envelope glycoprotein complex was studied by sedimentation gradient centrifugation analyses of detergent-solubilized wild-type and mutant envelope (env) gene products. These studies show that the envelope glycoprotein forms an oligomer during biosynthesis, which is most likely a trimer, and that this is the form of the complex found in virions. Our results are consistent with oligomer formation and transport out of the endoplasmic reticulum being closely linked. From analyses of mutant envelope proteins we conclude that the extracellular domain of the glycoprotein is sufficient for oligomer formation but that the transmembrane domain is required to stabilize this complex. Additional experiments suggest that interactions between external domains of the membrane-spanning, gp37 polypeptides are those most important for the formation of trimers. The significance of these observations to retroviral replication and implications for antiviral drug development are discussed.

Full text

PDF
8688

Images in this article

8689Image
on p.8689
8690Image
on p.8690
8690Image
on p.8690
8690Image
on p.8690
8690Image
on p.8690
8691Image
on p.8691
8691Image
on p.8691
8691Image
on p.8691

Selected References

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

  1. Bolognesi D. P., Bauer H., Gelderblom H., Hüper G. Polypeptides of avian RNA tumor viruses. IV. Components of the viral envelope. Virology. 1972 Mar;47(3):551–566. doi: 10.1016/0042-6822(72)90545-4. [DOI] [PubMed] [Google Scholar]
  2. Davis G. L., Hunter E. A charged amino acid substitution within the transmembrane anchor of the Rous sarcoma virus envelope glycoprotein affects surface expression but not intracellular transport. J Cell Biol. 1987 Sep;105(3):1191–1203. doi: 10.1083/jcb.105.3.1191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Doms R. W., Keller D. S., Helenius A., Balch W. E. Role for adenosine triphosphate in regulating the assembly and transport of vesicular stomatitis virus G protein trimers. J Cell Biol. 1987 Nov;105(5):1957–1969. doi: 10.1083/jcb.105.5.1957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gebhardt A., Bosch J. V., Ziemiecki A., Friis R. R. Rous sarcoma virus p19 and gp35 can be chemically crosslinked to high molecular weight complexes. An insight into virus assembly. J Mol Biol. 1984 Apr 5;174(2):297–317. doi: 10.1016/0022-2836(84)90340-1. [DOI] [PubMed] [Google Scholar]
  5. Germain R. N., Bentley D. M., Quill H. Influence of allelic polymorphism on the assembly and surface expression of class II MHC (Ia) molecules. Cell. 1985 Nov;43(1):233–242. doi: 10.1016/0092-8674(85)90028-5. [DOI] [PubMed] [Google Scholar]
  6. Gething M. J., McCammon K., Sambrook J. Expression of wild-type and mutant forms of influenza hemagglutinin: the role of folding in intracellular transport. Cell. 1986 Sep 12;46(6):939–950. doi: 10.1016/0092-8674(86)90076-0. [DOI] [PubMed] [Google Scholar]
  7. Gething M. J., Sambrook J. Construction of influenza haemagglutinin genes that code for intracellular and secreted forms of the protein. Nature. 1982 Dec 16;300(5893):598–603. doi: 10.1038/300598a0. [DOI] [PubMed] [Google Scholar]
  8. Hardwick J. M., Shaw K. E., Wills J. W., Hunter E. Amino-terminal deletion mutants of the Rous sarcoma virus glycoprotein do not block signal peptide cleavage but can block intracellular transport. J Cell Biol. 1986 Sep;103(3):829–838. doi: 10.1083/jcb.103.3.829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hunter E. Biological techniques for avian sarcoma viruses. Methods Enzymol. 1979;58:379–393. doi: 10.1016/s0076-6879(79)58153-1. [DOI] [PubMed] [Google Scholar]
  10. Hunter E., Hill E., Hardwick M., Bhown A., Schwartz D. E., Tizard R. Complete sequence of the Rous sarcoma virus env gene: identification of structural and functional regions of its product. J Virol. 1983 Jun;46(3):920–936. doi: 10.1128/jvi.46.3.920-936.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Katz R. A., Omer C. A., Weis J. H., Mitsialis S. A., Faras A. J., Guntaka R. V. Restriction endonuclease and nucleotide sequence analyses of molecularly cloned unintegrated avian tumor virus DNA: structure of large terminal repeats in circle junctions. J Virol. 1982 Apr;42(1):346–351. doi: 10.1128/jvi.42.1.346-351.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kreis T. E., Lodish H. F. Oligomerization is essential for transport of vesicular stomatitis viral glycoprotein to the cell surface. Cell. 1986 Sep 12;46(6):929–937. doi: 10.1016/0092-8674(86)90075-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lazarides E., Moon R. T. Assembly and topogenesis of the spectrin-based membrane skeleton in erythroid development. Cell. 1984 Jun;37(2):354–356. doi: 10.1016/0092-8674(84)90364-7. [DOI] [PubMed] [Google Scholar]
  14. Leamnson R. N., Halpern M. S. Subunit structure of the glycoprotein complex of avian tumor virus. J Virol. 1976 Jun;18(3):956–968. doi: 10.1128/jvi.18.3.956-968.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lentz M. R., Air G. M. Loss of enzyme activity in a site-directed mutant of influenza neuraminidase compared to expressed wild-type protein. Virology. 1986 Jan 15;148(1):74–83. doi: 10.1016/0042-6822(86)90404-6. [DOI] [PubMed] [Google Scholar]
  16. Minami Y., Weissman A. M., Samelson L. E., Klausner R. D. Building a multichain receptor: synthesis, degradation, and assembly of the T-cell antigen receptor. Proc Natl Acad Sci U S A. 1987 May;84(9):2688–2692. doi: 10.1073/pnas.84.9.2688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Patarca R., Haseltine W. A. Similarities among retrovirus proteins. Nature. 1984 Dec 6;312(5994):496–496. doi: 10.1038/312496a0. [DOI] [PubMed] [Google Scholar]
  18. Pauli G., Rohde W., Harms E. The structure of the Rous sarcoma virus glycoprotein complex. Arch Virol. 1978;58(1):61–64. doi: 10.1007/BF01315536. [DOI] [PubMed] [Google Scholar]
  19. Pepinsky R. B., Cappiello D., Wilkowski C., Vogt V. M. Chemical crosslinking of proteins in avian sarcoma and leukemia viruses. Virology. 1980 Apr 15;102(1):205–210. doi: 10.1016/0042-6822(80)90081-1. [DOI] [PubMed] [Google Scholar]
  20. Perez L. G., Davis G. L., Hunter E. Mutants of the Rous sarcoma virus envelope glycoprotein that lack the transmembrane anchor and cytoplasmic domains: analysis of intracellular transport and assembly into virions. J Virol. 1987 Oct;61(10):2981–2988. doi: 10.1128/jvi.61.10.2981-2988.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Perez L. G., Hunter E. Mutations within the proteolytic cleavage site of the Rous sarcoma virus glycoprotein that block processing to gp85 and gp37. J Virol. 1987 May;61(5):1609–1614. doi: 10.1128/jvi.61.5.1609-1614.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Perez L., Wills J. W., Hunter E. Expression of the Rous sarcoma virus env gene from a simian virus 40 late-region replacement vector: effects of upstream initiation codons. J Virol. 1987 Apr;61(4):1276–1281. doi: 10.1128/jvi.61.4.1276-1281.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. White J., Matlin K., Helenius A. Cell fusion by Semliki Forest, influenza, and vesicular stomatitis viruses. J Cell Biol. 1981 Jun;89(3):674–679. doi: 10.1083/jcb.89.3.674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Wiley D. C., Skehel J. J. The structure and function of the hemagglutinin membrane glycoprotein of influenza virus. Annu Rev Biochem. 1987;56:365–394. doi: 10.1146/annurev.bi.56.070187.002053. [DOI] [PubMed] [Google Scholar]
  25. Wiley D. C., Skehel J. J., Waterfield M. Evidence from studies with a cross-linking reagent that the haemagglutinin of influenza virus is a trimer. Virology. 1977 Jun 15;79(2):446–448. doi: 10.1016/0042-6822(77)90371-3. [DOI] [PubMed] [Google Scholar]
  26. Wills J. W., Srinivas R. V., Hunter E. Mutations of the Rous sarcoma virus env gene that affect the transport and subcellular location of the glycoprotein products. J Cell Biol. 1984 Dec;99(6):2011–2023. doi: 10.1083/jcb.99.6.2011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wilson I. A., Skehel J. J., Wiley D. C. Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 A resolution. Nature. 1981 Jan 29;289(5796):366–373. doi: 10.1038/289366a0. [DOI] [PubMed] [Google Scholar]
  28. Yoshimura A., Kuroda K., Kawasaki K., Yamashina S., Maeda T., Ohnishi S. Infectious cell entry mechanism of influenza virus. J Virol. 1982 Jul;43(1):284–293. doi: 10.1128/jvi.43.1.284-293.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES