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Open data
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Basic information
Entry | Database: PDB / ID: 7c76 | ||||||
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Title | Cryo-EM structure of human TLR3 in complex with UNC93B1 | ||||||
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![]() | IMMUNE SYSTEM / Toll-like receptors / UNC93B1 / MFS | ||||||
Function / homology | ![]() 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 / toll-like receptor 7 signaling pathway / T cell antigen processing and presentation / regulation of dendritic cell cytokine production ...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 / toll-like receptor 7 signaling pathway / T cell antigen processing and presentation / 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 binding / activation of NF-kappaB-inducing kinase activity / toll-like receptor 3 signaling pathway / necroptotic signaling pathway / detection of virus / toll-like receptor 9 signaling pathway / RIP-mediated NFkB activation via ZBP1 / early phagosome / 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 / cellular response to exogenous dsRNA / response to exogenous dsRNA / negative regulation of osteoclast differentiation / positive regulation of interferon-alpha production / cellular response to interferon-beta / positive regulation of chemokine production / extrinsic apoptotic signaling pathway / JNK cascade / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / 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 / intracellular protein transport / microglial cell activation / cell morphogenesis / cellular response to virus / cellular response to type II interferon / positive regulation of inflammatory response / cellular response to mechanical stimulus / positive regulation of non-canonical NF-kappaB signal transduction / positive regulation of interleukin-6 production / positive regulation of angiogenesis / positive regulation of type II interferon production / transmembrane signaling receptor activity / antigen processing and presentation of exogenous peptide antigen via MHC class II / male gonad development / positive regulation of tumor necrosis factor 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 / lysosome / endosome membrane / endosome / defense response to bacterium / positive regulation of apoptotic process / Golgi membrane / lysosomal membrane / innate immune response / endoplasmic reticulum membrane / positive regulation of gene expression / signal transduction / endoplasmic reticulum / positive regulation of transcription by RNA polymerase II / extracellular space / identical protein binding / membrane / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.4 Å | ||||||
![]() | Ohto, U. / Ishida, H. / Shimizu, T. | ||||||
![]() | ![]() Title: Cryo-EM structures of Toll-like receptors in complex with UNC93B1. Authors: Hanako Ishida / Jinta Asami / Zhikuan Zhang / Tomohiro Nishizawa / Hideki Shigematsu / Umeharu Ohto / Toshiyuki Shimizu / ![]() Abstract: Nucleic acid-sensing Toll-like receptors (TLRs) play a pivotal role in innate immunity by recognizing foreign DNA and RNA. Compartmentalization of these TLRs in the endosome limits their activation ...Nucleic acid-sensing Toll-like receptors (TLRs) play a pivotal role in innate immunity by recognizing foreign DNA and RNA. Compartmentalization of these TLRs in the endosome limits their activation by self-derived nucleic acids and reduces the possibility of autoimmune reactions. Although chaperone Unc-93 homolog B1, TLR signaling regulator (UNC93B1) is indispensable for the trafficking of TLRs from the endoplasmic reticulum to the endosome, mechanisms of UNC93B1-mediated TLR regulation remain largely unknown. Here, we report two cryo-EM structures of human and mouse TLR3-UNC93B1 complexes and a human TLR7-UNC93B1 complex. UNC93B1 exhibits structural similarity to the major facilitator superfamily transporters. Both TLRs interact with the UNC93B1 amino-terminal six-helix bundle through their transmembrane and luminal juxtamembrane regions, but the complexes of TLR3 and TLR7 with UNC93B1 differ in their oligomerization state. The structural information provided here should aid in designing compounds to combat autoimmune diseases. | ||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 224.7 KB | Display | ![]() |
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PDB format | ![]() | 185.2 KB | Display | ![]() |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 30293MC ![]() 7c77C ![]() 7cynC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Assembly
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Components
#1: Protein | Mass: 103946.320 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||||||
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#2: Protein | Mass: 66695.969 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||||||
#3: 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 #4: Polysaccharide | Source method: isolated from a genetically manipulated source #5: Sugar | ChemComp-NAG / Has ligand of interest | N | |
-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
Component | Name: Complex of TLR3 and UNC93B1 / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 5.5 Details: 25 mM Hepes-NaOH, pH 7.5, 0.2 M NaCl, and 0.01% GDN |
Specimen | 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 | Cryogen name: ETHANE |
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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 |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
CTF correction | Type: NONE |
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3D reconstruction | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 134000 / Symmetry type: POINT |