Title : Structural reorganization of the
Toll-like receptor 8 dimer induced by agonistic ligands
Abstract :
- Toll-like receptor 7 7 (TLR7 ) and TLR8 recognize single-stranded RNA and initiate innate immune responses
- Several synthetic agonists of TLR7- TLR8 display novel therapeutic potential; however, the molecular basis for ligand recognition and activation of signaling by TLR7 or TLR8 is largely unknown
- In this study, the crystal structures of unliganded and ligand-induced activated human TLR8 dimers were elucidated
- Ligand recognition was mediated by a dimerization interface formed by two protomers
- Upon ligand stimulation, the TLR8 dimer was reorganized such that the two C termini were brought into proximity
- The loop between leucine leucine-rich repeat 14 (LRR14) and LRR15 was cleaved; however, the N- and C-terminal halves remained associated and contributed to ligand recognition and dimerization
- Thus, ligand binding induces reorganization of the TLR8 dimer , which enables downstream signaling processes