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Structure paper

TitleTLR3 forms a highly organized cluster when bound to a poly(I:C) RNA ligand.
Journal, issue, pagesNat Commun, Vol. 13, Issue 1, Page 6876, Year 2022
Publish dateNov 12, 2022
AuthorsChan Seok Lim / Yoon Ha Jang / Ga Young Lee / Gu Min Han / Hye Jin Jeong / Ji Won Kim / Jie-Oh Lee /
PubMed AbstractToll-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 ...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.
External linksNat Commun / PubMed:36371424 / PubMed Central
MethodsEM (single particle)
Resolution2.26 - 13.2 Å
Structure data

32844

7wv3

EMDB-32844, PDB-7wv3:
Toll-like receptor3 linear cluster
Method: EM (single particle) / Resolution: 2.26 Å

32845

7wv4

EMDB-32845, PDB-7wv4:
ectoTLR3-poly(I:C) cluster
Method: EM (single particle) / Resolution: 3.35 Å

32846

7wv5

EMDB-32846, PDB-7wv5:
ectoTLR3-poly(I:C)
Method: EM (single particle) / Resolution: 3.1 Å

32851

7wve

EMDB-32851, PDB-7wve:
CT-mut (D523K,D524K,E527K) TLR3-poly(I:C) complex
Method: EM (single particle) / Resolution: 3.11 Å

32852

7wvf

EMDB-32852, PDB-7wvf:
ectoTLR3-mAb12-poly(I:C) complex
Method: EM (single particle) / Resolution: 3.91 Å

32853

7wvj

EMDB-32853, PDB-7wvj:
NT-mut(K117D,K139D,K145D) TLR3 -poly I:C complex
Method: EM (single particle) / Resolution: 3.26 Å

EMDB-34361: TLR3(A795H)-poly(I:C) complex
Method: EM (single particle) / Resolution: 6.47 Å

EMDB-34367: TLR3-mAb12-poly(I:C)
Method: EM (single particle) / Resolution: 13.2 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • Human (human)
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsIMMUNE SYSTEM/RNA / Toll-like receptor / dsRNA / Innate immunity / Receptor / IMMUNE SYSTEM / IMMUNE SYSTEM-RNA complex

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