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
Wang, Q. & Carmichael, G.G. Microbiol. Mol. Biol. Rev. 68, 432–452 (2004).
Alexopoulou, L., Holt, A.C., Medzhitov, R. & Flavell, R.A. Nature 413, 732–738 (2001).
Fire, A. et al. Nature 391, 806–811 (1998).
Reynolds, A. et al. RNA 12, 988–993 (2006).
Kariko, K., Bhuyan, P., Capodici, J. & Weissman, D. J. Immunol. 172, 6545–6549 (2004).
Kleinman, M.E. et al. Nature 452, 591–597 (2008).
Bell, J.K. et al. J. Endotoxin Res. 12, 375–378 (2006).
Choe, J., Kelker, M.S. & Wilson, I.A. Science 309, 581–585 (2005).
Bell, J.K., Askins, J., Hall, P.R., Davies, D.R. & Segal, D.M. Proc. Natl. Acad. Sci. USA 103, 8792–8797 (2006).
Bell, J.K. et al. Proc. Natl. Acad. Sci. USA 102, 10976–10980 (2005).
Okahira, S. et al. DNA Cell Biol. 24, 614–623 (2005).
Bobst, A.M., Torrence, P.F., Kouidou, S. & Witkop, B. Proc. Natl. Acad. Sci. USA 73, 3788–3792 (1976).
Carter, W.A. et al. J. Mol. Biol. 70, 567–587 (1972).
Greene, J.J. et al. Biochemistry 17, 4214–4220 (1978).
Kakiuchi, N. et al. J. Biol. Chem. 257, 1924–1928 (1982).
Miles, D.L., Miles, D.W. & Eyring, H. Proc. Natl. Acad. Sci. USA 76, 1018–1021 (1979).
Liu, L. et al. Science 320, 379–381 (2008).
Leonard, J.N. et al. Proc. Natl. Acad. Sci. USA 105, 258–263 (2008).
Pieper, U. et al. Nucleic Acids Res. 34, D291–D295 (2006).
Judge, A.D., Bola, G., Lee, A.C. & MacLachlan, I. Mol. Ther. 13, 494–505 (2006).
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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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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DOI: https://doi.org/10.1038/nsmb.1453