Editors' ChoiceStructural Biology

Dissecting TLR8 Interactions

Science Signaling  26 Mar 2013:
Vol. 6, Issue 268, pp. ec74
DOI: 10.1126/scisignal.2004168

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. 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.

H. Tanji, U. Ohto, T. Shibata, K. Miyake, T. Shimizu, Structural reorganization of the Toll-like receptor 8 dimer induced by agonistic ligands. Science 339, 1426–1429 (2013). [Abstract] [Full Text]