Quaternary structure of influenza virus hemagglutinin after acid treatment - PubMed (original) (raw)

Quaternary structure of influenza virus hemagglutinin after acid treatment

R W Doms et al. J Virol. 1986 Dec.

Abstract

Hemagglutinin (HA), a trimeric spike glycoprotein of influenza virus, mediates fusion between the viral envelope and the membrane of an endosome during virus entry. Fusion is triggered by low pH, which induces an irreversible conformational change in the protein. Several studies have indicated that intersubunit contacts along the trimer interfaces may be broken during this alteration. To determine whether HA dissociates into individual subunits as a consequence of the conformational change, we used velocity gradient sedimentation in the presence of Triton X-100. We also determined the resistance of acid-treated HA to dissociation by sodium dodecyl sulfate, a property of the HA trimer. At pH 7.0, isolated HA sedimented as a 9S trimer and gave the characteristic trimer pattern after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. After acidification the HA remained trimeric irrespective of whether it was exposed to acid in intact virus particles or in solubilized form. Only when very low concentrations of HA were acidified did a fraction dissociate to dimers and monomers. In contrast, the water-soluble ectodomain fragment of HA (BHA) readily dissociated under a variety of conditions. Negative-stain electron microscopy supported the notion that HA molecules in virus particles do not dissociate upon acidification and may form larger oligomeric structures in the plane of the viral membrane. Taken together, the results suggested that it is the trimeric HA, or higher-order structures thereof, that are active in the acid-induced fusion reaction. Further, the results emphasized the role of the transmembrane anchors of HA in preventing dissociation of the trimer.

PubMed Disclaimer

Similar articles

• Studies on the structure of the influenza virus haemagglutinin at the pH of membrane fusion.
  Ruigrok RW, Aitken A, Calder LJ, Martin SR, Skehel JJ, Wharton SA, Weis W, Wiley DC. Ruigrok RW, et al. J Gen Virol. 1988 Nov;69 ( Pt 11):2785-95. doi: 10.1099/0022-1317-69-11-2785. J Gen Virol. 1988. PMID: 3183628
• Membrane fusion activity of the influenza virus hemagglutinin. The low pH-induced conformational change.
  Doms RW, Helenius A, White J. Doms RW, et al. J Biol Chem. 1985 Mar 10;260(5):2973-81. J Biol Chem. 1985. PMID: 3972812
• Thermal denaturation of influenza virus and its relationship to membrane fusion.
  Epand RM, Epand RF. Epand RM, et al. Biochem J. 2002 Aug 1;365(Pt 3):841-8. doi: 10.1042/BJ20020290. Biochem J. 2002. PMID: 11994048 Free PMC article.
• Early steps of the conformational change of influenza virus hemagglutinin to a fusion active state: stability and energetics of the hemagglutinin.
  Huang Q, Sivaramakrishna RP, Ludwig K, Korte T, Böttcher C, Herrmann A. Huang Q, et al. Biochim Biophys Acta. 2003 Jul 11;1614(1):3-13. doi: 10.1016/s0005-2736(03)00158-5. Biochim Biophys Acta. 2003. PMID: 12873761 Review.
• Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin.
  Skehel JJ, Wiley DC. Skehel JJ, et al. Annu Rev Biochem. 2000;69:531-69. doi: 10.1146/annurev.biochem.69.1.531. Annu Rev Biochem. 2000. PMID: 10966468 Review.

Cited by

• Analyzing the fusion process of influenza hemagglutinin by mutagenesis and molecular modeling.
  Guy HR, Durell SR, Schoch C, Blumenthal R. Guy HR, et al. Biophys J. 1992 Apr;62(1):95-7. doi: 10.1016/S0006-3495(92)81790-3. Biophys J. 1992. PMID: 1600107 Free PMC article. No abstract available.
• A mutation in the human immunodeficiency virus type 1 transmembrane glycoprotein gp41 dominantly interferes with fusion and infectivity.
  Freed EO, Delwart EL, Buchschacher GL Jr, Panganiban AT. Freed EO, et al. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):70-4. doi: 10.1073/pnas.89.1.70. Proc Natl Acad Sci U S A. 1992. PMID: 1729720 Free PMC article.
• Antibody-forming cell response to virus challenge in mice immunized with DNA encoding the influenza virus hemagglutinin.
  Justewicz DM, Morin MJ, Robinson HL, Webster RG. Justewicz DM, et al. J Virol. 1995 Dec;69(12):7712-7. doi: 10.1128/JVI.69.12.7712-7717.1995. J Virol. 1995. PMID: 7494280 Free PMC article.
• Expression and analysis of presenilin 1 in a human neuronal system: localization in cell bodies and dendrites.
  Cook DG, Sung JC, Golde TE, Felsenstein KM, Wojczyk BS, Tanzi RE, Trojanowski JQ, Lee VM, Doms RW. Cook DG, et al. Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):9223-8. doi: 10.1073/pnas.93.17.9223. Proc Natl Acad Sci U S A. 1996. PMID: 8799182 Free PMC article.
• The B-cell response in lymphoid tissue of mice immunized with various antigenic forms of the influenza virus hemagglutinin.
  Justewicz DM, Doherty PC, Webster RG. Justewicz DM, et al. J Virol. 1995 Sep;69(9):5414-21. doi: 10.1128/JVI.69.9.5414-5421.1995. J Virol. 1995. PMID: 7636986 Free PMC article.

References

1. 1. Nature. 1983 Jul 7-13;304(5921):76-8 - PubMed
2. 1. Virology. 1983 Apr 30;126(2):587-99 - PubMed
3. 1. J Cell Biol. 1986 Jan;102(1):11-23 - PubMed
4. 1. J Biol Chem. 1961 May;236:1372-9 - PubMed
5. 1. EMBO J. 1986 Jan;5(1):41-9 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Atypon
  • Europe PubMed Central
  • PubMed Central

• Other Literature Sources

  • The Lens - Patent Citations Database