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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | ectoTLR3-mAb12-poly(I:C) complex | |||||||||
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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 / 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 / endolysosome membrane / hyperosmotic response / positive regulation of cytokine production involved in inflammatory response / Trafficking and processing of endosomal TLR / positive regulation of macrophage cytokine production / RSV-host interactions / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Lim CS / Jang YH / Lee GY / Han GM / Lee JO | |||||||||
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
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 168.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 15 KB 15 KB | Display Display | ![]() |
Images | ![]() | 52.8 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7wvfMC ![]() 7wv3C ![]() 7wv4C ![]() 7wv5C ![]() 7wveC ![]() 7wvjC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 1.0865 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : ectoTLR3-mAb12-poly(I:C) complex
Entire | Name: ectoTLR3-mAb12-poly(I:C) complex |
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Components |
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-Supramolecule #1: ectoTLR3-mAb12-poly(I:C) complex
Supramolecule | Name: ectoTLR3-mAb12-poly(I:C) complex / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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-Supramolecule #2: ectoTLR3-mAb12
Supramolecule | Name: ectoTLR3-mAb12 / type: complex / Chimera: Yes / ID: 2 / Parent: 1 / Macromolecule list: #1, #4 |
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Source (natural) | Organism: ![]() ![]() |
-Supramolecule #3: poly(I:C)
Supramolecule | Name: poly(I:C) / type: complex / Chimera: Yes / ID: 3 / Parent: 1 / Macromolecule list: #2-#3 |
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-Macromolecule #1: Toll-like receptor 3
Macromolecule | Name: Toll-like receptor 3 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 78.423375 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: ADPKCTVSHE VADCSHLKLT QVPDDLPTNI TVLNLTHNQL RRLPAANFTR YSQLTSLDVG FNTISKLEPE LCQKLPMLKV LNLQHNELS QLSDKTFAFC TNLTELHLMS NSIQKIKNNP FVKQKNLITL DLSHNGLSST KLGTQVQLEN LQELLLSNNK I QALKSEEL ...String: ADPKCTVSHE VADCSHLKLT QVPDDLPTNI TVLNLTHNQL RRLPAANFTR YSQLTSLDVG FNTISKLEPE LCQKLPMLKV LNLQHNELS QLSDKTFAFC TNLTELHLMS NSIQKIKNNP FVKQKNLITL DLSHNGLSST KLGTQVQLEN LQELLLSNNK I QALKSEEL DIFANSSLKK LELSSNQIKE FSPGCFHAIG RLFGLFLNNV QLGPSLTEKL CLELANTSIR NLSLSNSQLS TT SNTTFLG LKWTNLTMLD LSYNNLNVVG NDSFAWLPQL EYFFLEYNNI QHLFSHSLHG LFNVRYLNLK RSFTKQSISL ASL PKIDDF SFQWLKCLEH LNMEDNDIPG IKSNMFTGLI NLKYLSLSNS FTSLRTLTNE TFVSLAHSPL HILNLTKNKI SKIE SDAFS WLGHLEVLDL GLNEIGQELT GQEWRGLENI FEIYLSYNKY LQLTRNSFAL VPSLQRLMLR RVALKNVDSS PSPFQ PLRN LTILDLSNNN IANINDDMLE GLEKLEILDL QHNNLARLWK HANPGGPIYF LKGLSHLHIL NLESNGFDEI PVEVFK DLF ELKIIDLGLN NLNTLPASVF NNQVSLKSLN LQKNLITSVE KKVFGPAFRN LTELDMRFNP FDCTCESIAW FVNWINE TH TNIPELSSHY LCNTPPHYHG FPVRLFDTSS CKSGRLVPRG SHHHHHH |
-Macromolecule #4: mAb12
Macromolecule | Name: mAb12 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 27.712111 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: ADPQVQLQQS GPGLVKPSQT LSLTCAISGD SVSSNSAAWG WIRQSPGRGL EWLGIIQKRS KWYNNYAVSV KSRITINPDT SKNQFSLQL NSVTPEDTAV YYCARYSYPF YSIDYWGQGT LVTVSSGGGG SGGGGSGGGG SGGGGSQSVL TQPPSVSVAP G QTARISCS ...String: ADPQVQLQQS GPGLVKPSQT LSLTCAISGD SVSSNSAAWG WIRQSPGRGL EWLGIIQKRS KWYNNYAVSV KSRITINPDT SKNQFSLQL NSVTPEDTAV YYCARYSYPF YSIDYWGQGT LVTVSSGGGG SGGGGSGGGG SGGGGSQSVL TQPPSVSVAP G QTARISCS GDNIGSYYVH WYQQKPGQAP VLVIYEDSER PSGIPERFSG SNSGNTATLT ISGTQAEDEA DYYCSSYDDP NF QVFGGGT KLTVLGHHHH HHHH |
-Macromolecule #2: RNA (46-MER)
Macromolecule | Name: RNA (46-MER) / type: rna / ID: 2 / Number of copies: 1 |
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Source (natural) | Organism: synthetic construct (others) |
Molecular weight | Theoretical: 13.993408 KDa |
Sequence | String: CCCCCCCCCC CCCCCCCCCC CCCCCCCCCC CCCCCCCCCC CCCCCC |
-Macromolecule #3: RNA (46-MER)
Macromolecule | Name: RNA (46-MER) / type: rna / ID: 3 / Number of copies: 1 |
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Source (natural) | Organism: synthetic construct (others) |
Molecular weight | Theoretical: 15.143821 KDa |
Sequence | String: IIIIIIIIII IIIIIIIIII IIIIIIIIII IIIIIIIIII IIIIII |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Concentration | 1.0 mg/mL | |||||||||
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Buffer | pH: 5.5 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec. / Pretreatment - Atmosphere: AIR | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | TFS GLACIOS |
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Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 40.0 e/Å2 |
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Image processing
Initial angle assignment | Type: OTHER |
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Final angle assignment | Type: OTHER |
Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.91 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 136835 |