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Brief Communication

Nature Structural & Molecular Biology 15, 761–763 (1 July 2008) | doi:10.1038/nsmb.1453

A second binding site for double-stranded RNA in TLR3 and consequences for interferon activation

Nina Pirher , Karolina Ivi|[ccaron]|ak , Jelka Pohar , Mojca Ben|[ccaron]|ina & Roman Jerala

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 |[Aring]|. 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.