A second binding site for double-stranded RNA in TLR3 and consequences for interferon activation (original) (raw)

Nature Structural & Molecular Biology volume 15, pages 761–763 (2008)Cite this article

Abstract

We show that substrate specificity of Toll-like receptor 3 (TLR3) is due to the presence of two binding sites in the ectodomain, separated by 50 Å. This corresponds to two turns of a double-stranded RNA duplex, allowing differentiation between nucleic acids in the A- or B-type conformation. We propose that there are different arrangements of TLR3 ectodomains along the double-stranded RNA that could modulate the strength of the interferon response.

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References

  1. Wang, Q. & Carmichael, G.G. Microbiol. Mol. Biol. Rev. 68, 432–452 (2004).
    Article CAS Google Scholar
  2. Alexopoulou, L., Holt, A.C., Medzhitov, R. & Flavell, R.A. Nature 413, 732–738 (2001).
    Article CAS Google Scholar
  3. Fire, A. et al. Nature 391, 806–811 (1998).
    Article CAS Google Scholar
  4. Reynolds, A. et al. RNA 12, 988–993 (2006).
    Article CAS Google Scholar
  5. Kariko, K., Bhuyan, P., Capodici, J. & Weissman, D. J. Immunol. 172, 6545–6549 (2004).
    Article CAS Google Scholar
  6. Kleinman, M.E. et al. Nature 452, 591–597 (2008).
    Article CAS Google Scholar
  7. Bell, J.K. et al. J. Endotoxin Res. 12, 375–378 (2006).
    Article CAS Google Scholar
  8. Choe, J., Kelker, M.S. & Wilson, I.A. Science 309, 581–585 (2005).
    Article CAS Google Scholar
  9. Bell, J.K., Askins, J., Hall, P.R., Davies, D.R. & Segal, D.M. Proc. Natl. Acad. Sci. USA 103, 8792–8797 (2006).
    Article CAS Google Scholar
  10. Bell, J.K. et al. Proc. Natl. Acad. Sci. USA 102, 10976–10980 (2005).
    Article CAS Google Scholar
  11. Okahira, S. et al. DNA Cell Biol. 24, 614–623 (2005).
    Article CAS Google Scholar
  12. Bobst, A.M., Torrence, P.F., Kouidou, S. & Witkop, B. Proc. Natl. Acad. Sci. USA 73, 3788–3792 (1976).
    Article CAS Google Scholar
  13. Carter, W.A. et al. J. Mol. Biol. 70, 567–587 (1972).
    Article CAS Google Scholar
  14. Greene, J.J. et al. Biochemistry 17, 4214–4220 (1978).
    Article CAS Google Scholar
  15. Kakiuchi, N. et al. J. Biol. Chem. 257, 1924–1928 (1982).
    CAS PubMed Google Scholar
  16. Miles, D.L., Miles, D.W. & Eyring, H. Proc. Natl. Acad. Sci. USA 76, 1018–1021 (1979).
    Article CAS Google Scholar
  17. Liu, L. et al. Science 320, 379–381 (2008).
    Article CAS Google Scholar
  18. Leonard, J.N. et al. Proc. Natl. Acad. Sci. USA 105, 258–263 (2008).
    Article CAS Google Scholar
  19. Pieper, U. et al. Nucleic Acids Res. 34, D291–D295 (2006).
    Article CAS Google Scholar
  20. Judge, A.D., Bola, G., Lee, A.C. & MacLachlan, I. Mol. Ther. 13, 494–505 (2006).
    Article CAS Google Scholar

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Acknowledgements

This work was funded by the Slovenian Research Agency. We would like to thank J. Hiscott (McGill University) for his kind gift of interferon-β luciferase reporter plasmid.

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Authors and Affiliations

  1. Department of Biotechnology, National Institute of Chemistry, Hajdrihova 19, Ljubljana, 1000, Slovenia
    Nina Pirher, Karolina Ivičak, Jelka Pohar, Mojca Benčina & Roman Jerala
  2. Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, 1000, Slovenia
    Roman Jerala

Authors

  1. Nina Pirher
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  2. Karolina Ivičak
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  3. Jelka Pohar
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  4. Mojca Benčina
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  5. Roman Jerala
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Corresponding author

Correspondence toRoman Jerala.

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Pirher, N., Ivičak, K., Pohar, J. et al. A second binding site for double-stranded RNA in TLR3 and consequences for interferon activation.Nat Struct Mol Biol 15, 761–763 (2008). https://doi.org/10.1038/nsmb.1453

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