Skip to main content

Some NLM-NCBI services and products are experiencing heavy traffic, which may affect performance and availability. We apologize for the inconvenience and appreciate your patience. For assistance, please contact our Help Desk at info@ncbi.nlm.nih.gov.

The EMBO Journal logoLink to The EMBO Journal
. 1986 Jan;5(1):41–49. doi: 10.1002/j.1460-2075.1986.tb04175.x

Electron microscopy of the low pH structure of influenza virus haemagglutinin.

R W Ruigrok, N G Wrigley, L J Calder, S Cusack, S A Wharton, E B Brown, J J Skehel
PMCID: PMC1166693  PMID: 3956479

Abstract

Influenza virus haemagglutinin mediates infection of cells by fusion of viral and endosomal membranes, triggered by low pH which induces a conformational change in the protein. We report studies of this change by electron microscopy, neutron scattering, sedimentation and photon correlation on X-31 (H3N2) haemagglutinin, both intact and bromelain cleaved, in various assemblies. HAs in all preparations showed a thinning at low pH, and a marked elongation which was removed on tryptic digestion, revealing altered features in the remaining stem portion of the molecule. A tentative model of the change is proposed, with reference to the known X-ray structure at neutral pH, in which major changes occur in the stem tertiary structure, while the top portion is only affected in its quaternary structure.

Full text

PDF
41

Images in this article

Selected References

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

  1. Booy F. P., Ruigrok R. W., van Bruggen E. F. Electron microscopy of influenza virus. A comparison of negatively stained and ice-embedded particles. J Mol Biol. 1985 Aug 20;184(4):667–676. doi: 10.1016/0022-2836(85)90312-2. [DOI] [PubMed] [Google Scholar]
  2. Brand C. M., Skehel J. J. Crystalline antigen from the influenza virus envelope. Nat New Biol. 1972 Aug 2;238(83):145–147. doi: 10.1038/newbio238145a0. [DOI] [PubMed] [Google Scholar]
  3. Daniels R. S., Douglas A. R., Skehel J. J., Wiley D. C. Analyses of the antigenicity of influenza haemagglutinin at the pH optimum for virus-mediated membrane fusion. J Gen Virol. 1983 Aug;64(Pt 8):1657–1662. doi: 10.1099/0022-1317-64-8-1657. [DOI] [PubMed] [Google Scholar]
  4. Daniels R. S., Downie J. C., Hay A. J., Knossow M., Skehel J. J., Wang M. L., Wiley D. C. Fusion mutants of the influenza virus hemagglutinin glycoprotein. Cell. 1985 Feb;40(2):431–439. doi: 10.1016/0092-8674(85)90157-6. [DOI] [PubMed] [Google Scholar]
  5. Dopheide T. A., Ward C. W. The location of the bromelain cleavage site in a Hong Kong influenza virus Haemagglutinin. J Gen Virol. 1981 Feb;52(Pt 2):367–370. doi: 10.1099/0022-1317-52-2-367. [DOI] [PubMed] [Google Scholar]
  6. FOLCH J., LEES M., SLOANE STANLEY G. H. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957 May;226(1):497–509. [PubMed] [Google Scholar]
  7. Huang R. T., Rott R., Klenk H. D. Influenza viruses cause hemolysis and fusion of cells. Virology. 1981 Apr 15;110(1):243–247. doi: 10.1016/0042-6822(81)90030-1. [DOI] [PubMed] [Google Scholar]
  8. Klenk H. D., Rott R., Orlich M., Blödorn J. Activation of influenza A viruses by trypsin treatment. Virology. 1975 Dec;68(2):426–439. doi: 10.1016/0042-6822(75)90284-6. [DOI] [PubMed] [Google Scholar]
  9. Lazarowitz S. G., Choppin P. W. Enhancement of the infectivity of influenza A and B viruses by proteolytic cleavage of the hemagglutinin polypeptide. Virology. 1975 Dec;68(2):440–454. doi: 10.1016/0042-6822(75)90285-8. [DOI] [PubMed] [Google Scholar]
  10. Ruigrok R. W., Cremers A. F., Beyer W. E., de Ronde-Verloop F. M. Changes in the morphology of influenza particles induced at low pH. Arch Virol. 1984;82(3-4):181–194. doi: 10.1007/BF01311162. [DOI] [PubMed] [Google Scholar]
  11. Skehel J. J., Bayley P. M., Brown E. B., Martin S. R., Waterfield M. D., White J. M., Wilson I. A., Wiley D. C. Changes in the conformation of influenza virus hemagglutinin at the pH optimum of virus-mediated membrane fusion. Proc Natl Acad Sci U S A. 1982 Feb;79(4):968–972. doi: 10.1073/pnas.79.4.968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. White J., Kielian M., Helenius A. Membrane fusion proteins of enveloped animal viruses. Q Rev Biophys. 1983 May;16(2):151–195. doi: 10.1017/s0033583500005072. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Wiley D. C., Wilson I. A., Skehel J. J. Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation. Nature. 1981 Jan 29;289(5796):373–378. doi: 10.1038/289373a0. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Wrigley N. G., Brown E., Chillingworth R. K. Combining accurate defocus with low-dose imaging in high resolution electron microscopy of biological material. J Microsc. 1983 May;130(Pt 2):225–232. doi: 10.1111/j.1365-2818.1983.tb04220.x. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES