Toll-like receptors recognize molecules associated with pathogens and initiate inflammatory responses. For example, Toll-like receptor 3 (TLR3) recognizes double-stranded RNA (dsRNA), an intermediate viral replication. The TLR3 ectodomain binds as a dimer to dsRNA, but the molecular basis for signaling remains unclear. Liu et al . now report the structure of a complex between two mouse TLR3 ectodomains and dsRNA. Two horseshoe-shaped TLR3-ectodomain monomers bind to opposite faces of the dsRNA through their N and C termini and dimerize through their C termini so that the N termini are at opposite ends of the linear dsRNA molecule. This dimerization mode could mediate signal transduction by facilitating dimerization of the receptor cytoplasmic domains. L. Liu, I. Botos, Y. Wang, J. N. Leonard, J. Shiloach, D. M. Segal, D. R. Davies, Structural basis of Toll-like receptor 3 signaling with double-stranded RNA. Science 320 , 379-381 (2008). [Abstract] [Full Text]