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Open data
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Basic information
Entry | Database: PDB / ID: 7wv3 | |||||||||
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Title | Toll-like receptor3 linear cluster | |||||||||
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![]() | IMMUNE SYSTEM/RNA / Toll-like receptor / dsRNA / Innate immunity / Receptor / IMMUNE SYSTEM / IMMUNE SYSTEM-RNA complex | |||||||||
Function / homology | ![]() TLR3 deficiency - HSE / response to dsRNA / UNC93B1 deficiency - HSE / TICAM1 deficiency - HSE / type III interferon production / positive regulation of type III interferon production / TRAF3 deficiency - HSE / regulation of dendritic cell cytokine production / I-kappaB phosphorylation / Toll Like Receptor 3 (TLR3) Cascade ...TLR3 deficiency - HSE / response to dsRNA / UNC93B1 deficiency - HSE / TICAM1 deficiency - HSE / type III interferon production / positive regulation of type III interferon production / TRAF3 deficiency - HSE / regulation of dendritic cell cytokine production / I-kappaB phosphorylation / Toll Like Receptor 3 (TLR3) Cascade / TLR3-mediated TICAM1-dependent programmed cell death / inflammatory response to wounding / activation of NF-kappaB-inducing kinase activity / toll-like receptor 3 signaling pathway / detection of virus / necroptotic signaling pathway / RIP-mediated NFkB activation via ZBP1 / hyperosmotic response / endolysosome membrane / positive regulation of cytokine production involved in inflammatory response / Trafficking and processing of endosomal TLR / positive regulation of macrophage cytokine production / toll-like receptor signaling pathway / pattern recognition receptor activity / cellular response to exogenous dsRNA / RSV-host interactions / response to exogenous dsRNA / negative regulation of osteoclast differentiation / ubiquitin-like protein ligase binding / positive regulation of interferon-alpha production / cellular response to interferon-beta / positive regulation of chemokine production / extrinsic apoptotic signaling pathway / JNK cascade / positive regulation of interleukin-12 production / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / extracellular matrix / TICAM1,TRAF6-dependent induction of TAK1 complex / TICAM1-dependent activation of IRF3/IRF7 / positive regulation of interferon-beta production / TICAM1, RIP1-mediated IKK complex recruitment / positive regulation of interleukin-8 production / positive regulation of JNK cascade / microglial cell activation / positive regulation of non-canonical NF-kappaB signal transduction / cellular response to virus / cellular response to type II interferon / positive regulation of interleukin-6 production / positive regulation of type II interferon production / cellular response to mechanical stimulus / positive regulation of inflammatory response / male gonad development / positive regulation of angiogenesis / positive regulation of tumor necrosis factor production / transmembrane signaling receptor activity / cellular response to xenobiotic stimulus / double-stranded RNA binding / signaling receptor activity / defense response to virus / positive regulation of canonical NF-kappaB signal transduction / early endosome / endosome membrane / defense response to bacterium / positive regulation of apoptotic process / Golgi membrane / lysosomal membrane / innate immune response / positive regulation of gene expression / endoplasmic reticulum membrane / signal transduction / positive regulation of transcription by RNA polymerase II / extracellular space / identical protein binding / membrane / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() synthetic construct (others) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.26 Å | |||||||||
![]() | Lim, C.S. / Jang, Y.H. / Lee, G.Y. / Han, G.M. / Lee, J.O. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: TLR3 forms a highly organized cluster when bound to a poly(I:C) RNA ligand. Authors: Chan Seok Lim / Yoon Ha Jang / Ga Young Lee / Gu Min Han / Hye Jin Jeong / Ji Won Kim / Jie-Oh Lee / ![]() 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 ...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. | |||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 575.5 KB | Display | ![]() |
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PDB format | ![]() | 454 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 32844MC ![]() 7wv4C ![]() 7wv5C ![]() 7wveC ![]() 7wvfC ![]() 7wvjC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 102376.281 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #2: RNA chain | | Mass: 24369.598 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) #3: RNA chain | | Mass: 26370.277 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) #4: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #5: Sugar | ChemComp-NAG / Has ligand of interest | N | Has protein modification | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
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Molecular weight | Experimental value: NO | ||||||||||||||||||||||||
Source (natural) | Organism: ![]() | ||||||||||||||||||||||||
Source (recombinant) | Organism: ![]() | ||||||||||||||||||||||||
Buffer solution | pH: 5.5 | ||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 7.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 | ||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2100 nm / Nominal defocus min: 700 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 2.26 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 982514 / Symmetry type: POINT |
Atomic model building | Protocol: RIGID BODY FIT |
Atomic model building | PDB-ID: 3ULU Accession code: 3ULU / Source name: PDB / Type: experimental model |