+Open data
-Basic information
Entry | Database: PDB / ID: 7wv3 | |||||||||
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Title | Toll-like receptor3 linear cluster | |||||||||
Components |
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Keywords | IMMUNE SYSTEM/RNA / Toll-like receptor / dsRNA / Innate immunity / Receptor / IMMUNE SYSTEM / IMMUNE SYSTEM-RNA complex | |||||||||
Function / homology | Function and homology information TLR3 deficiency - HSE / UNC93B1 deficiency - HSE / TICAM1 deficiency - HSE / type III interferon production / positive regulation of type III interferon production / response to dsRNA / TRAF3 deficiency - HSE / regulation of dendritic cell cytokine production / Toll Like Receptor 3 (TLR3) Cascade / I-kappaB phosphorylation ...TLR3 deficiency - HSE / UNC93B1 deficiency - HSE / TICAM1 deficiency - HSE / type III interferon production / positive regulation of type III interferon production / response to dsRNA / TRAF3 deficiency - HSE / regulation of dendritic cell cytokine production / Toll Like Receptor 3 (TLR3) Cascade / I-kappaB phosphorylation / TLR3-mediated TICAM1-dependent programmed cell death / inflammatory response to wounding / toll-like receptor 3 signaling pathway / necroptotic signaling pathway / detection of virus / activation of NF-kappaB-inducing kinase activity / 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 / pattern recognition receptor activity / toll-like receptor signaling pathway / RSV-host interactions / response to exogenous dsRNA / cellular response to exogenous dsRNA / negative regulation of osteoclast differentiation / positive regulation of interferon-alpha production / cellular response to interferon-beta / extrinsic apoptotic signaling pathway / positive regulation of chemokine production / JNK cascade / TICAM1,TRAF6-dependent induction of TAK1 complex / TICAM1-dependent activation of IRF3/IRF7 / positive regulation of interleukin-12 production / positive regulation of interferon-beta production / TICAM1, RIP1-mediated IKK complex recruitment / extracellular matrix / positive regulation of interleukin-8 production / positive regulation of JNK cascade / microglial cell activation / cellular response to virus / cellular response to type II interferon / positive regulation of inflammatory response / positive regulation of non-canonical NF-kappaB signal transduction / cellular response to mechanical stimulus / positive regulation of angiogenesis / transmembrane signaling receptor activity / positive regulation of interleukin-6 production / positive regulation of tumor necrosis factor production / male gonad development / positive regulation of type II interferon production / double-stranded RNA binding / cellular response to xenobiotic stimulus / signaling receptor activity / positive regulation of canonical NF-kappaB signal transduction / defense response to virus / early endosome / endosome membrane / defense response to bacterium / positive regulation of apoptotic process / lysosomal membrane / Golgi membrane / innate immune response / positive regulation of gene expression / endoplasmic reticulum membrane / signal transduction / positive regulation of transcription by RNA polymerase II / extracellular space / membrane / identical protein binding / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) synthetic construct (others) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.26 Å | |||||||||
Authors | Lim, C.S. / Jang, Y.H. / Lee, G.Y. / Han, G.M. / Lee, J.O. | |||||||||
Funding support | Korea, Republic Of, 2items
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Citation | Journal: Nat Commun / Year: 2022 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: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7wv3.cif.gz | 567.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7wv3.ent.gz | 453.9 KB | Display | PDB format |
PDBx/mmJSON format | 7wv3.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7wv3_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 7wv3_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 7wv3_validation.xml.gz | 73.2 KB | Display | |
Data in CIF | 7wv3_validation.cif.gz | 114.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wv/7wv3 ftp://data.pdbj.org/pub/pdb/validation_reports/wv/7wv3 | HTTPS FTP |
-Related structure data
Related structure data | 32844MC 7wv4C 7wv5C 7wveC 7wvfC 7wvjC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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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.) Homo sapiens (human) / Gene: TLR3 / Cell line (production host): HEK293s GnTi- / Production host: Homo sapiens (human) / References: UniProt: O15455 #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 | |
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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 |
-Sample preparation
Component |
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Molecular weight | Experimental value: NO | ||||||||||||||||||||||||
Source (natural) | Organism: Human (human) | ||||||||||||||||||||||||
Source (recombinant) | Organism: Homo sapiens (human) | ||||||||||||||||||||||||
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 |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
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) |
-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 |