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-Structure paper
タイトル | TLR3 forms a highly organized cluster when bound to a poly(I:C) RNA ligand. |
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ジャーナル・号・ページ | Nat Commun, Vol. 13, Issue 1, Page 6876, Year 2022 |
掲載日 | 2022年11月12日 |
著者 | Chan Seok Lim / Yoon Ha Jang / Ga Young Lee / Gu Min Han / Hye Jin Jeong / Ji Won Kim / Jie-Oh Lee / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Commun / PubMed:36371424 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.26 - 13.2 Å |
構造データ | EMDB-32844, PDB-7wv3: EMDB-32845, PDB-7wv4: EMDB-32846, PDB-7wv5: EMDB-32851, PDB-7wve: EMDB-32852, PDB-7wvf: EMDB-32853, PDB-7wvj: EMDB-34361: TLR3(A795H)-poly(I:C) complex EMDB-34367: TLR3-mAb12-poly(I:C) |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | IMMUNE SYSTEM/RNA / Toll-like receptor / dsRNA / Innate immunity / Receptor / IMMUNE SYSTEM / IMMUNE SYSTEM-RNA complex |