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- PDB-6lw1: 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: PDB / ID: 6lw1 | ||||||
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Title | Cryo-EM structure of TLR7/Cpd-7 (DSR-139970) complex in open form | ||||||
![]() | Toll-like receptor 7 | ||||||
![]() | IMMUNE SYSTEM / TLR7 / antagonist | ||||||
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 | ELECTRON MICROSCOPY / 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
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 275.8 KB | Display | ![]() |
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PDB format | ![]() | 228.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 999.2 KB | Display | ![]() |
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Full document | ![]() | 1 MB | Display | |
Data in XML | ![]() | 47.1 KB | Display | |
Data in CIF | ![]() | 70.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 30002MC ![]() 0999C ![]() 1000C ![]() 6lvxC ![]() 6lvyC ![]() 6lvzC ![]() 6lw0C M: map data used to model this data 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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Components
#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.) ![]() ![]() ![]() ![]() #2: Chemical | Has ligand of interest | Y | |
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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 |
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Sample preparation
Component | Name: TLR7/Cpd-7 (DSR-139970) complex / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT | ||||||||||||
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Molecular weight | Value: 0.2 MDa / Experimental value: NO | ||||||||||||
Source (natural) |
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Source (recombinant) | Organism: ![]() ![]() | ||||||||||||
Buffer solution | pH: 4.8 | ||||||||||||
Specimen | Conc.: 0.8 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||
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: TFS 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
Software | Name: PHENIX / Version: 1.17.1_3660: / Classification: refinement | ||||||||||||||||||||||||
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EM software | Name: RELION / Version: 3 / Category: 3D reconstruction | ||||||||||||||||||||||||
CTF correction | Type: NONE | ||||||||||||||||||||||||
Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 301212 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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