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- EMDB-30002: Cryo-EM structure of TLR7/Cpd-7 (DSR-139970) complex in open form -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-30002 | |||||||||
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Title | Cryo-EM structure of TLR7/Cpd-7 (DSR-139970) complex in open form | |||||||||
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Function / homology | ![]() toll-like receptor 7 signaling pathway / response to cGMP / siRNA binding / early phagosome / positive regulation of macrophage cytokine production / pattern recognition receptor activity / toll-like receptor signaling pathway / canonical NF-kappaB signal transduction / positive regulation of interferon-alpha production / positive regulation of chemokine production ...toll-like receptor 7 signaling pathway / response to cGMP / siRNA binding / early phagosome / positive regulation of macrophage cytokine production / pattern recognition receptor activity / toll-like receptor signaling pathway / canonical NF-kappaB signal transduction / positive regulation of interferon-alpha production / positive regulation of chemokine production / JNK cascade / positive regulation of interferon-beta production / positive regulation of interleukin-8 production / regulation of protein phosphorylation / cellular response to virus / positive regulation of non-canonical NF-kappaB signal transduction / cellular response to mechanical stimulus / positive regulation of interleukin-6 production / double-stranded RNA binding / positive regulation of type II interferon production / defense response to virus / single-stranded RNA binding / lysosome / receptor complex / endosome / inflammatory response / innate immune response / endoplasmic reticulum / positive regulation of transcription by RNA polymerase II / metal ion binding / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.8 Å | |||||||||
![]() | Zhang Z / Ohto U / Shimizu T | |||||||||
![]() | ![]() Title: Structural analysis reveals TLR7 dynamics underlying antagonism. Authors: Shingo Tojo / Zhikuan Zhang / Hiroyuki Matsui / Masahiro Tahara / Mitsunori Ikeguchi / Mami Kochi / Mami Kamada / Hideki Shigematsu / Akihisa Tsutsumi / Naruhiko Adachi / Takuma Shibata / ...Authors: Shingo Tojo / Zhikuan Zhang / Hiroyuki Matsui / Masahiro Tahara / Mitsunori Ikeguchi / Mami Kochi / Mami Kamada / Hideki Shigematsu / Akihisa Tsutsumi / Naruhiko Adachi / Takuma Shibata / Masaki Yamamoto / Masahide Kikkawa / Toshiya Senda / Yoshiaki Isobe / Umeharu Ohto / Toshiyuki Shimizu / ![]() Abstract: Toll-like receptor 7 (TLR7) recognizes both microbial and endogenous RNAs and nucleosides. Aberrant activation of TLR7 has been implicated in several autoimmune diseases including systemic lupus ...Toll-like receptor 7 (TLR7) recognizes both microbial and endogenous RNAs and nucleosides. Aberrant activation of TLR7 has been implicated in several autoimmune diseases including systemic lupus erythematosus (SLE). Here, by modifying potent TLR7 agonists, we develop a series of TLR7-specific antagonists as promising therapeutic agents for SLE. These compounds protect mice against lethal autoimmunity. Combining crystallography and cryo-electron microscopy, we identify the open conformation of the receptor and reveal the structural equilibrium between open and closed conformations that underlies TLR7 antagonism, as well as the detailed mechanism by which TLR7-specific antagonists bind to their binding pocket in TLR7. Our work provides small-molecule TLR7-specific antagonists and suggests the TLR7-targeting strategy for treating autoimmune diseases. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 38 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 10.9 KB 10.9 KB | Display Display | ![]() |
Images | ![]() | 240 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 471 KB | Display | ![]() |
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Full document | ![]() | 470.6 KB | Display | |
Data in XML | ![]() | 5.8 KB | Display | |
Data in CIF | ![]() | 6.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6lw1MC ![]() 0999C ![]() 1000C ![]() 6lvxC ![]() 6lvyC ![]() 6lvzC ![]() 6lw0C M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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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: 0.996 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : TLR7/Cpd-7 (DSR-139970) complex
Entire | Name: TLR7/Cpd-7 (DSR-139970) complex |
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Components |
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-Supramolecule #1: TLR7/Cpd-7 (DSR-139970) complex
Supramolecule | Name: TLR7/Cpd-7 (DSR-139970) complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() ![]() |
Molecular weight | Theoretical: 200 KDa |
-Macromolecule #1: Toll-like receptor 7
Macromolecule | Name: Toll-like receptor 7 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 94.745594 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: RSPWARWFPK TLPCDVTLDV SKNHVIVDCT DKHLTEIPGG IPTNTTNLTL TINHIPDISP ASFHRLVHLV EIDFRCNCVP IRLGSKSNM CPRRLQIKPR SFSGLTYLKS LYLDGNQLLE IPQGLPPSLQ LLSLEANNIF SIRKEQLTEL ANIEILYLGQ N CYYRNPCY ...String: RSPWARWFPK TLPCDVTLDV SKNHVIVDCT DKHLTEIPGG IPTNTTNLTL TINHIPDISP ASFHRLVHLV EIDFRCNCVP IRLGSKSNM CPRRLQIKPR SFSGLTYLKS LYLDGNQLLE IPQGLPPSLQ LLSLEANNIF SIRKEQLTEL ANIEILYLGQ N CYYRNPCY VSYSIEKDAF LNLTKLKVLS LKDNNVTTVP TVLPSTLTEL YLYNNMIAEI QEDDFNNLNQ LQILDLSGNC PR CYNAPFP CTPCKNNSPL QIPVNAFDAL TELKVLRLHS NSLQHVPPRW FKNINNLQEL DLSQNFLAKE IGDAKFLHFL PNL IQLDLS FNFELQVYRA SMNLSQAFSS LKSLKILRIR GYVFKELKSF QLSPLHNLQN LEVLDLGTNF IKIANLSMFK QFKR LKVID LSVNKISPSG DSLVPRGSSN ARTSVESYEP QVLEQLYYFR YDKYARSCRF KNKEASFTSV QESCYKYGQT LDLSK NSIF FIKSSDFQHL SFLKCLNLSG NLISQTLNGS EFQPLAELRY LDFSNNRLDL LHSTAFEELR KLEVLDISSN SHYFQS EGI THMLNFTKNL KVLQKLMMND NDISSSTSRT MESESLRTLE FRGNHLDVLW RDGDNRYLQL FKNLLKLEEL DISKNSL SF LPSGVFDGMP PNLKNLSLAK NGLKSFIWEK LRYLKNLETL DLSHNQLTTV PERLSNCSRS LKNLILKNNQ IRSLTKYF L QDAFQLRYLD LSSNKIQMIQ KTSFPENVLN NLKMLLLHHN RFLCTCDAVW FVWWVQHTEV TIPYLATDVT CVGPGAHKG QSVISLDLYT CELDLTNEFL VPR |
-Macromolecule #2: 2-ethoxy-8-(5-fluoranylpyridin-3-yl)-6-methyl-9-[[4-[[(1S,4S)-5-m...
Macromolecule | Name: 2-ethoxy-8-(5-fluoranylpyridin-3-yl)-6-methyl-9-[[4-[[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]methyl]phenyl]methyl]purine type: ligand / ID: 2 / Number of copies: 2 / Formula: EX3 |
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Molecular weight | Theoretical: 487.572 Da |
Chemical component information | ![]() ChemComp-EX3: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.8 mg/mL |
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Buffer | pH: 4.8 |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Applied symmetry - Point group: C2 (2 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3.0) / Number images used: 301212 |
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Initial angle assignment | Type: NOT APPLICABLE |
Final angle assignment | Type: NOT APPLICABLE |