Structural basis of toll-like receptor 3 signaling with double-stranded RNA

Lin Liu, Istvan Botos, Yan Wang, Joshua N. Leonard, Joseph Shiloach, David M. Segal, David R. Davies

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475 Scopus citations

Abstract

Toll-like receptor 3 (TLR3) recognizes double-stranded RNA (dsRNA), a molecular signature of most viruses, and triggers inflammatory responses that prevent viral spread. TLR3 ectodomains (ECDs) dimerize on oligonucleotides of at least 40 to 50 base pairs in length, the minimal length required for signal transduction. To establish the molecular basis for ligand binding and signaling, we determined the crystal structure of a complex between two mouse TLR3-ECDs and dsRNA at 3.4 angstrom resolution. Each TLR3-ECD binds dsRNA at two sites located at opposite ends of the TLR3 horseshoe, and an intermolecular contact between the two TLR3-ECD C-terminal domains coordinates and stabilizes the dimer. This juxtaposition could mediate downstream signaling by dimerizing the cytoplasmic Toll interleukin-1 receptor (TIR) domains. The overall shape of the TLR3-ECD does not change upon binding to dsRNA.

Original languageEnglish (US)
Pages (from-to)379-381
Number of pages3
JournalScience
Volume320
Issue number5874
DOIs
StatePublished - Apr 18 2008

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Cite this

Liu, L., Botos, I., Wang, Y., Leonard, J. N., Shiloach, J., Segal, D. M., & Davies, D. R. (2008). Structural basis of toll-like receptor 3 signaling with double-stranded RNA. Science, 320(5874), 379-381. https://doi.org/10.1126/science.1155406