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Open data
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Basic information
Entry | Database: PDB / ID: 6lvx | ||||||
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Title | Crystal structure of TLR7/Cpd-1 (SM-374527) complex | ||||||
![]() | Toll-like receptor 7 | ||||||
![]() | IMMUNE SYSTEM / TLR7 / agonist | ||||||
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 / positive regulation of type II interferon production / double-stranded RNA binding / 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 | ![]() ![]() ![]() | ||||||
![]() | 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. | ||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 324 KB | Display | ![]() |
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PDB format | ![]() | 259.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.3 MB | Display | ![]() |
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Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 53 KB | Display | |
Data in CIF | ![]() | 73 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 0999C ![]() 1000C ![]() 6lvyC ![]() 6lvzC ![]() 6lw0C ![]() 6lw1C ![]() 5gmhS S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Component-ID: _ / Ens-ID: 1 / Beg auth comp-ID: ALA / Beg label comp-ID: ALA / End auth comp-ID: LEU / End label comp-ID: LEU / Refine code: _ / Auth seq-ID: 27 - 835 / Label seq-ID: 5 - 813
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Components
-Protein , 1 types, 2 molecules AB
#1: Protein | Mass: 94745.594 Da / Num. of mol.: 2 Mutation: N145Q/N367Q/S418L/E419VV420P/G421R/F422G/C423S/N466Q/N777Q Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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-Sugars , 2 types, 12 molecules ![](data/chem/img/NAG.gif)
#2: 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 |
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#4: Sugar | ChemComp-NAG / |
-Non-polymers , 3 types, 54 molecules ![](data/chem/img/EWL.gif)
![](data/chem/img/SO4.gif)
![](data/chem/img/HOH.gif)
![](data/chem/img/SO4.gif)
![](data/chem/img/HOH.gif)
#3: Chemical | #5: Chemical | ChemComp-SO4 / #6: Water | ChemComp-HOH / | |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.68 Å3/Da / Density % sol: 54.09 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop Details: PEG3350 or PEG8000, ammonium sulfate, sodium citrate pH 5.0, Tris-HCl pH 7.5, NaCl |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS PILATUS3 S 2M / Detector: PIXEL / Date: Nov 18, 2016 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.77→50.01 Å / Num. obs: 52528 / % possible obs: 100 % / Redundancy: 13 % / CC1/2: 0.994 / Net I/σ(I): 27.4 |
Reflection shell | Resolution: 2.77→2.86 Å / Num. unique obs: 4507 / CC1/2: 0.959 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 5GMH Resolution: 2.77→50.01 Å / Cor.coef. Fo:Fc: 0.904 / Cor.coef. Fo:Fc free: 0.861 / SU B: 13.158 / SU ML: 0.258 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.359 Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 135.33 Å2 / Biso mean: 34.391 Å2 / Biso min: 6.34 Å2
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Refinement step | Cycle: final / Resolution: 2.77→50.01 Å
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Refine LS restraints |
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Refine LS restraints NCS | Ens-ID: 1 / Number: 103780 / Refine-ID: X-RAY DIFFRACTION / Type: interatomic distance / Rms dev position: 0.03 Å / Weight position: 0.05
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LS refinement shell | Resolution: 2.77→2.842 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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