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Structure of influenza haemagglutinin at the pH of membrane fusion

Abstract

Low pH induces a conformational change in the influenza virus haemagglutinin, which then mediates fusion of the viral and host cell membranes. The three-dimensional structure of a fragment of the haemagglutinin in this conformation reveals a major refolding of the secondary and tertiary structure of the molecule. The apolar fusion peptide moves at least 100 Å to one tip of the molecule. At the other end a helical segment unfolds, a subdomain relocates reversing the chain direction, and part of the structure becomes disordered.

References

  1. 1

    Wiley, D. C. & Skehel, J. J. A. Rev. Biochem. 56, 365–394 (1987).

    CAS  Article  Google Scholar 

  2. 2

    Maeda, T. & Ohnishi, S. FEBS Lett. 122, 283–287 (1980).

    CAS  Article  Google Scholar 

  3. 3

    Huang, R. T. C., Rott, R. & Klenk, H.-D. Virology 110, 243–247 (1981).

    CAS  Article  Google Scholar 

  4. 4

    White, J., Matlin, K. & Helenius, A. J. Cell Biol. 89, 674–679 (1982).

    Article  Google Scholar 

  5. 5

    White, J. M. & Wilson, I. A. J. Cell Biol. 105, 2887–2896 (1987).

    CAS  Article  Google Scholar 

  6. 6

    Godley, L. et al. Cell 68, 635–645 (1992).

    CAS  Article  Google Scholar 

  7. 7

    Brand, C. M. & Skehel, J. J. Nature new Biol. 238, 145–147 (1972).

    CAS  Article  Google Scholar 

  8. 8

    Skehel, J. J. & Waterfield, M. D. Proc. natn. Acad. Sci. U.S.A. 72, 93–97 (1975).

    ADS  CAS  Article  Google Scholar 

  9. 9

    Wilson, I. A., Skehel, J. J. & Wiley, D. C. Nature 289, 366–373 (1981).

    ADS  CAS  Article  Google Scholar 

  10. 10

    Weis, W. I., Brünger, A. T., Skehel, J. J. & Wiley, D. C. J. molec. Biol. 212, 737–761 (1990).

    CAS  Article  Google Scholar 

  11. 11

    Skehel, J. J. et al. Proc. natn. Acad. Sci. U.S.A. 79, 968–972 (1982).

    ADS  CAS  Article  Google Scholar 

  12. 12

    Gething, M.-J., Doms, R. W., York, D. & White, J. J. Cell Biol. 102, 11–23 (1986).

    CAS  Article  Google Scholar 

  13. 13

    Daniels, R. S. et al. in The Origin of Pandemic Influenza Viruses (eds Laver, G. W. & Chu, C. M.) 1–7 (Elsevier-North Holland, New York, 1985).

    Google Scholar 

  14. 14

    Doms, R. W., Helenius, A. & White, J. J. biol. Chem. 260, 2973–2981 (1985).

    CAS  PubMed  Google Scholar 

  15. 15

    Ruigrok, R. W. H. et al. J. gen. Virol. 69, 2785–2795 (1988).

    CAS  Article  Google Scholar 

  16. 16

    Bullough, P. A. et al. J. molec. Biol. 236, 1262–1265 (1994).

    CAS  Article  Google Scholar 

  17. 17

    Brünger, A. T. Nature 355, 472–475 (1992).

    ADS  Article  Google Scholar 

  18. 18

    Wharton, S. A. et al. J. biol. Chem. 263, 4474–4480 (1988).

    CAS  PubMed  Google Scholar 

  19. 19

    Carr, C. M. & Kim, P. S. Cell 73, 823–832 (1993).

    CAS  Article  Google Scholar 

  20. 20

    Ward, C. W. & Dopheide, T. A. Aust. J. biol. Sci. 33, 441–447 (1980).

    CAS  Article  Google Scholar 

  21. 21

    Graves, P. N., Schulman, J. L., Young, J. F. & Palese, P. Virology 126, 106–116 (1983).

    CAS  Article  Google Scholar 

  22. 22

    Webster, R. G., Brown, L. E. & Jackson, D. C. Virology 126, 587–599 (1983).

    CAS  Article  Google Scholar 

  23. 23

    Daniels, R. S. et al. in The Origin of Pandemic Influenza Viruses (eds Laver, W. G. & Chu, C. M.) 8–18 (Elsevier-North Holland, New York, 1985).

    Google Scholar 

  24. 24

    Ruigrok, R. W. H. et al. EMBO J. 5, 41–49 (1986).

    CAS  Article  Google Scholar 

  25. 25

    Daniels, R. S. et al. EMBO J. 6, 1459–1465 (1987).

    CAS  Article  Google Scholar 

  26. 26

    Yewdell, J. W., Gerhard, W. & Bachi, T. J. Virol. 48, 239–248 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 27

    Ruigrok, R. W. H. et al. Virology 155, 484–497 (1986).

    CAS  Article  Google Scholar 

  28. 28

    Goldsmith, E. J. & Mottonen, J. Structure 2, 241–244 (1994).

    CAS  Article  Google Scholar 

  29. 29

    Crick, F. H. C. Acta crystallogr. 6, 689–697 (1953).

    CAS  Article  Google Scholar 

  30. 30

    McLachlan, A. D. & Karn, J. J. molec. Biol. 164, 605–626 (1983).

    CAS  Article  Google Scholar 

  31. 31

    Daniels, R. S. et al. Cell 40, 431–439 (1985).

    CAS  Article  Google Scholar 

  32. 32

    Sauter, N. K. et al. Biochemistry 31, 9609–9621 (1992).

    CAS  Article  Google Scholar 

  33. 33

    Stegmann, T. & Helenius, A. in Viral Fusion Mechanisms (ed. Bentz, J.) 89–111 (CRC Press, Boca Raton, Florida, 1993).

    Google Scholar 

  34. 34

    Söllner, T., Bennett, M. K., Whiteheart, S. W., Scheller, R. H. & Rothman, J. E. Cell 75, 409–418 (1993).

    Article  Google Scholar 

  35. 35

    Ellens, H., Bentz, J., Mason, D., Zhang, F. & White, J. M. Biochemistry 29, 9697–9707 (1990).

    CAS  Article  Google Scholar 

  36. 36

    Spruce, A. E., Iwata, A., White, J. M. & Almers, W. Nature 342, 555–558 (1989).

    ADS  CAS  Article  Google Scholar 

  37. 37

    Kemble, G. W., Danieli, T. & White, J. M. Cell 76, 383–391 (1994).

    CAS  Article  Google Scholar 

  38. 38

    Blum, M., Metcalf, P., Harrison, S. C. & Wiley, D. C. J. appl. Crystallogr. 20, 235–242 (1987).

    CAS  Article  Google Scholar 

  39. 39

    Leslie, A. G. W. in CCP4 and ESF-EACMB Newsletter on Protein Crystallography, No. 26 (Daresbury Laboratory, Warrington, 1992).

    Google Scholar 

  40. 40

    CCP4, A Suite of Programs for Protein Crystallography (SERC (UK) Collaborative Computing Project No. 4, Daresbury Laboratory, Warrington, 1979).

  41. 41

    Terwilliger, T. C. & Eisenberg, D. Acta crystallogr. A39, 813–817 (1983).

    Article  Google Scholar 

  42. 42

    Metcalf, P., Blum, M., Freymann, D., Turner, M. & Wiley, D. C. Nature 325, 84–86 (1987).

    ADS  CAS  Article  Google Scholar 

  43. 43

    Bricogne, G. Acta crystallogr. A32, 832–847 (1976).

    Article  Google Scholar 

  44. 44

    Jones, T. A., Zou, J.-Y., Cowan, S. W. & Kjeldgaard, M. Acta crystallogr. A47, 110–119 (1991).

    Article  Google Scholar 

  45. 45

    Brünger, A. T. X-PLOR (Version 3.1): A System for X-ray Crystallography and NMR (Yale Univ. Press, New Haven, 1992).

    Google Scholar 

  46. 46

    Lüthy, R., Bowie, J. U. & Eisenberg, D. Nature 356, 83–85 (1992).

    ADS  Article  Google Scholar 

  47. 47

    Colovos, C. & Yeates, T. O. Prot. Sci. 2, 1511–1519 (1993).

    CAS  Article  Google Scholar 

  48. 48

    Read, R. J. Acta crystallogr. A42, 140–149 (1986).

    Article  Google Scholar 

  49. 49

    Kraulis, P. J. appl. Crystallogr. 24, 924–950 (1991).

    Article  Google Scholar 

  50. 50

    Carson, M. J. molec. Graphics 5, 103–106 (1987).

    CAS  Article  Google Scholar 

Download references

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Bullough, P., Hughson, F., Skehel, J. et al. Structure of influenza haemagglutinin at the pH of membrane fusion. Nature 371, 37–43 (1994). https://doi.org/10.1038/371037a0

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