Title : Structural basis of
toll-like receptor 3 signaling with double-stranded RNA
Abstract :
- Toll-like receptor 3 ( TLR3 ) recognizes double-stranded RNA (dsRNA), a molecular signature of most viruses, and triggers inflammatory responses that prevent viral spread
- TLR3 ectodomains (ECDs) dimerize on oligonucleotides of at least 40 to 50 base pairs in length, the minimal length required for signal transduction
- To establish the molecular basis for ligand binding and signaling, we determined the crystal structure of a complex between two mouse TLR3-ECDs and dsRNA at 3 .4 angstrom resolution
- Each TLR3- ECD binds dsRNA at two sites located at opposite ends of the TLR3 horseshoe, and an intermolecular contact between the two TLR3- ECD C-terminal domains coordinates and stabilizes the dimer
- This juxta position could mediate downstream signaling by dimerizing the cytoplasmic Toll interleukin-1 receptor ( TIR ) domains
- The overall shape of the TLR3- ECD does not change upon binding to dsRNA