Abstract
The exposure of the flavivirus tick-borne encephalitis (TBE) virus to an acidic pH is necessary for virus-induced membrane fusion and leads to a quantitative and irreversible conversion of the envelope protein E dimers to trimers. To study the structural requirements for this oligomeric rearrangement, the effect of low-pH treatment on the oligomeric state of different isolated forms of protein E was investigated. Full-length E dimers obtained by solubilization of virus with the detergent Triton X-100 formed trimers at low pH, whereas truncated E dimers lacking the stem-anchor region underwent a reversible dissociation into monomers without forming trimers. These data suggest that the low-pH-induced rearrangement in virions is a two-step process involving a reversible dissociation of the E dimers followed by an irreversible formation of trimers, a process which requires the stem-anchor portion of the protein. This region contains potential amphipathic alpha-helical and conserved structural elements whose interactions may contribute to the rearrangements which initiate the fusion process.
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- Allison S. L., Schalich J., Stiasny K., Mandl C. W., Kunz C., Heinz F. X. Oligomeric rearrangement of tick-borne encephalitis virus envelope proteins induced by an acidic pH. J Virol. 1995 Feb;69(2):695–700. doi: 10.1128/jvi.69.2.695-700.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Buckland R., Wild F. Leucine zipper motif extends. Nature. 1989 Apr 13;338(6216):547–547. doi: 10.1038/338547a0. [DOI] [PubMed] [Google Scholar]
- Bullough P. A., Hughson F. M., Skehel J. J., Wiley D. C. Structure of influenza haemagglutinin at the pH of membrane fusion. Nature. 1994 Sep 1;371(6492):37–43. doi: 10.1038/371037a0. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Gallagher T. M., Escarmis C., Buchmeier M. J. Alteration of the pH dependence of coronavirus-induced cell fusion: effect of mutations in the spike glycoprotein. J Virol. 1991 Apr;65(4):1916–1928. doi: 10.1128/jvi.65.4.1916-1928.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Gaudin Y., Ruigrok R. W., Brunner J. Low-pH induced conformational changes in viral fusion proteins: implications for the fusion mechanism. J Gen Virol. 1995 Jul;76(Pt 7):1541–1556. doi: 10.1099/0022-1317-76-7-1541. [DOI] [PubMed] [Google Scholar]
- Guirakhoo F., Heinz F. X., Kunz C. Epitope model of tick-borne encephalitis virus envelope glycoprotein E: analysis of structural properties, role of carbohydrate side chain, and conformational changes occurring at acidic pH. Virology. 1989 Mar;169(1):90–99. doi: 10.1016/0042-6822(89)90044-5. [DOI] [PubMed] [Google Scholar]
- Heinz F. X., Allison S. L., Stiasny K., Schalich J., Holzmann H., Mandl C. W., Kunz C. Recombinant and virion-derived soluble and particulate immunogens for vaccination against tick-borne encephalitis. Vaccine. 1995 Dec;13(17):1636–1642. doi: 10.1016/0264-410x(95)00133-l. [DOI] [PubMed] [Google Scholar]
- Heinz F. X., Kunz C. Chemical crosslinking of tick-borne encephalitis virus and its subunits. J Gen Virol. 1980 Feb;46(2):301–309. doi: 10.1099/0022-1317-46-2-301. [DOI] [PubMed] [Google Scholar]
- Heinz F. X., Kunz C. Formation of polymeric glycoprotein complexes from a flavivirus: tick-borne encephalitis virus. J Gen Virol. 1980 Jul;49(1):125–132. doi: 10.1099/0022-1317-49-1-125. [DOI] [PubMed] [Google Scholar]
- Heinz F. X., Kunz C. Homogeneity of the structural glycoprotein from European isolates of tick-borne encephalitis virus: comparison with other flaviviruses. J Gen Virol. 1981 Dec;57(Pt 2):263–274. doi: 10.1099/0022-1317-57-2-263. [DOI] [PubMed] [Google Scholar]
- Heinz F. X., Kunz C. Isolation of dimeric glycoprotein subunits from tick-borne encephalitis virus. Intervirology. 1980;13(3):169–177. doi: 10.1159/000149122. [DOI] [PubMed] [Google Scholar]
- Heinz F. X., Mandl C. W., Holzmann H., Kunz C., Harris B. A., Rey F., Harrison S. C. The flavivirus envelope protein E: isolation of a soluble form from tick-borne encephalitis virus and its crystallization. J Virol. 1991 Oct;65(10):5579–5583. doi: 10.1128/jvi.65.10.5579-5583.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heinz F. X., Stiasny K., Püschner-Auer G., Holzmann H., Allison S. L., Mandl C. W., Kunz C. Structural changes and functional control of the tick-borne encephalitis virus glycoprotein E by the heterodimeric association with protein prM. Virology. 1994 Jan;198(1):109–117. doi: 10.1006/viro.1994.1013. [DOI] [PubMed] [Google Scholar]
- Helenius A. Alphavirus and flavivirus glycoproteins: structures and functions. Cell. 1995 Jun 2;81(5):651–653. doi: 10.1016/0092-8674(95)90523-5. [DOI] [PubMed] [Google Scholar]
- Holzmann H., Stiasny K., York H., Dorner F., Kunz C., Heinz F. X. Tick-borne encephalitis virus envelope protein E-specific monoclonal antibodies for the study of low pH-induced conformational changes and immature virions. Arch Virol. 1995;140(2):213–221. doi: 10.1007/BF01309857. [DOI] [PubMed] [Google Scholar]
- Kielian M., Jungerwirth S. Mechanisms of enveloped virus entry into cells. Mol Biol Med. 1990 Feb;7(1):17–31. [PubMed] [Google Scholar]
- Lamb R. A. Paramyxovirus fusion: a hypothesis for changes. Virology. 1993 Nov;197(1):1–11. doi: 10.1006/viro.1993.1561. [DOI] [PubMed] [Google Scholar]
- Lu M., Blacklow S. C., Kim P. S. A trimeric structural domain of the HIV-1 transmembrane glycoprotein. Nat Struct Biol. 1995 Dec;2(12):1075–1082. doi: 10.1038/nsb1295-1075. [DOI] [PubMed] [Google Scholar]
- Mandl C. W., Heinz F. X., Kunz C. Sequence of the structural proteins of tick-borne encephalitis virus (western subtype) and comparative analysis with other flaviviruses. Virology. 1988 Sep;166(1):197–205. doi: 10.1016/0042-6822(88)90161-4. [DOI] [PubMed] [Google Scholar]
- Marsh M., Helenius A. Virus entry into animal cells. Adv Virus Res. 1989;36:107–151. doi: 10.1016/S0065-3527(08)60583-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rey F. A., Heinz F. X., Mandl C., Kunz C., Harrison S. C. The envelope glycoprotein from tick-borne encephalitis virus at 2 A resolution. Nature. 1995 May 25;375(6529):291–298. doi: 10.1038/375291a0. [DOI] [PubMed] [Google Scholar]
- Roehrig J. T., Hunt A. R., Johnson A. J., Hawkes R. A. Synthetic peptides derived from the deduced amino acid sequence of the E-glycoprotein of Murray Valley encephalitis virus elicit antiviral antibody. Virology. 1989 Jul;171(1):49–60. doi: 10.1016/0042-6822(89)90509-6. [DOI] [PubMed] [Google Scholar]
- Roehrig J. T., Johnson A. J., Hunt A. R., Bolin R. A., Chu M. C. Antibodies to dengue 2 virus E-glycoprotein synthetic peptides identify antigenic conformation. Virology. 1990 Aug;177(2):668–675. doi: 10.1016/0042-6822(90)90532-v. [DOI] [PubMed] [Google Scholar]
- Rost B., Sander C. Combining evolutionary information and neural networks to predict protein secondary structure. Proteins. 1994 May;19(1):55–72. doi: 10.1002/prot.340190108. [DOI] [PubMed] [Google Scholar]
- White J. M. Viral and cellular membrane fusion proteins. Annu Rev Physiol. 1990;52:675–697. doi: 10.1146/annurev.ph.52.030190.003331. [DOI] [PubMed] [Google Scholar]
- 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]
- de Groot R. J., Luytjes W., Horzinek M. C., van der Zeijst B. A., Spaan W. J., Lenstra J. A. Evidence for a coiled-coil structure in the spike proteins of coronaviruses. J Mol Biol. 1987 Aug 20;196(4):963–966. doi: 10.1016/0022-2836(87)90422-0. [DOI] [PMC free article] [PubMed] [Google Scholar]