7WV3

Toll-like receptor3 linear cluster

Summary for 7WV3

• Entry DOI: 10.2210/pdb7wv3/pdb
• Related: 7WV4 7WV5 7WVE 7WVF 7WVJ
• EMDB information: 32844
• Descriptor: Toll-like receptor 3, RNA (80-MER), 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: toll-like receptor, dsrna, innate immunity, receptor, immune system, immune system-rna complex, immune system/rna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 469834.03

Authors

Lim, C.S.,Jang, Y.H.,Lee, G.Y.,Han, G.M.,Lee, J.O. (deposition date: 2022-02-09, release date: 2022-11-16, Last modification date: 2024-10-30)

Primary citation

Lim, C.S.,Jang, Y.H.,Lee, G.Y.,Han, G.M.,Jeong, H.J.,Kim, J.W.,Lee, J.O.
TLR3 forms a highly organized cluster when bound to a poly(I:C) RNA ligand.
Nat Commun, 13:6876-6876, 2022

PubMed 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.

PubMed: 36371424
DOI: 10.1038/s41467-022-34602-0

Experimental method

ELECTRON MICROSCOPY (2.26 Å)