Summary information and primary citation
- PDB-id
-
7wv5;
SNAP-derived features in text and
JSON formats
- Class
- immune system-RNA
- Method
- cryo-EM (3.1 Å)
- Summary
- Ectotlr3-poly(i:c)
- Reference
-
Lim CS, Jang YH, Lee GY, Han GM, Jeong HJ, Kim JW, Lee JO
(2022): "TLR3 forms
a highly organized cluster when bound to a poly(I:C) RNA
ligand." Nat Commun, 13,
6876. doi: 10.1038/s41467-022-34602-0.
- Abstract
- Toll-like Receptor 3 (TLR3) initiates a potent
anti-viral immune response by binding to double-stranded
RNA ligands. Previous crystallographic studies showed that
TLR3 forms a homodimer when bound to a 46-base pair RNA
ligand. However, this short RNA fails to initiate a robust
immune response. To obtain structural insights into the
length dependency of TLR3 ligands, we determine the
cryo-electron microscopy structure of full-length TLR3 in a
complex with a synthetic RNA ligand with an average length
of ~400 base pairs. In the structure, the dimeric TLR3
units are clustered along the double-stranded RNA helix in
a highly organized and cooperative fashion with a uniform
inter-dimer spacing of 103 angstroms. The intracellular and
transmembrane domains are dispensable for the clustering
because their deletion does not interfere with the cluster
formation. Our structural observation suggests that
ligand-induced clustering of TLR3 dimers triggers the
ordered assembly of intracellular signaling adaptors and
initiates a robust innate immune response.
