The Toll-like receptors（TLRs）are a family of pattern-recognition receptors that recognize pathogen-associated molecular patterns and activate innate immune system. TLR8 is activated by single-stranded RNA or synthetic imidazoquinoline compounds. We determined the crystal structures of unliganded and liganded TLR8 to clarify signaling and activation mechanism of TLR8.
TLR8 monomer was ring-shaped structure in which N- and C-termini interacted directly. Both in the unliganded and liganded forms, TLR8 formed m-shaped dimer in which two C termini converged in the middle. Ligands were located in the two equivalent positions in the dimerization interface related by the non-crystallographic two-fold axis. The C-termini of the two TLR8 protomers were separated by 53 Å in the unliganded form; whereas, C-termini of the two monomers were brought into close proximity（～30 Å）in the liganded form, which would enable the subsequent dimerization of the TIR domains and downstream signaling.