Structural Reorganization of the Toll-Like Receptor 8 Dimer Induced by Agonistic Ligands

Dissecting TLR8 Interactions Toll-like receptors (TLRs) activate the innate immune system in response to invading pathogens. TLR7 and TLR8 recognize single-stranded RNA from viruses and also contribute to the pathogenesis of autoimmune diseases. Tanji et al. (p. 1426 ) now report the crystal structure of the unliganded TLR8 ectodomain and the TLR8 ectodomain bound to three different small-molecule agonists. Ligand binding to preformed TLR8 dimers induced conformational changes that brought the C-terminal domains closer together, presumably initiating downstream signaling.